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Biomedical subjects

G Weitzner

Publications and source records attributed to G Weitzner.

7 recordsLinked to original sources

Evidence for different clinical subtypes of type 1 diabetes mellitus: a prospective study.

The purpose of this study was to determine whether the sex, age, severity of clinical presentation, presence of ICAs, IAs, and HLA-DR and DQ types could predict, in a cohort of newly-diagnosed diabetic children: (1) the duration of beta-cell function as measured by C-peptide response to a Sustacal meal; and (2) determine if those predictors could identify disease subtypes. A cohort of 170 consecutive patients was followed for 60 months after diagnosis. We found that age (0.0029), sex (0.0136), ICA (0.0001), presence of DKA (0.0070) and C-peptide peak at diagnosis (0.0000) significantly predicted the duration of residual beta-cell function over time. Furthermore, C-peptide secretion at diagnosis, presence of ICA, age and sex allowed the identification of three different prognostic groups with varying acceleration of beta-cell loss.

Adolescent↗

Factors predicting course of beta-cell function in IDDM.

OBJECTIVE: The purpose of this study was to determine whether the severity o clinical presentation, sex, age, HLA type, and the presence of IAs and ICAs could predict the variation of residual insulin secretion as measured by the serum C-peptide response to a Sustacal meal. RESEARCH DESIGN AND METHODS: A cohort of 151 newly diagnosed IDDM children (mean age 10.2 +/- 4.6 yr) was followed prospectively for 3 yr. Thirty-five patients (12 males, 23 females) were still secreting C-peptide after 36 mo. RESULTS: We found that age (P = 0.0001), sex (P = 0.003), presence of ICA (P = 0.006), severity of clinical presentation (P = 0.001), and symptom duration (P = 0.002) significantly predicted the rate of loss of C-peptide secretion. The risks of accelerated C-peptide disappearance decreased with increasing age, the risk ratios being 0.25 for the older group (greater than 12 yr) compared with the younger group (less than 6 yr) and 0.50 for the intermediate group (6-12 yr) compared with the younger group. The risk for the presence of ICA was 1.7, and the risk for males was 1.7 also. There was a significant negative correlation between ICA titers and C-peptide at 18 and 24 mo after diagnosis (P = 0.04). There were no significant differences in HbA1 values between patients who secreted C-peptide and those who did not. CONCLUSIONS: We conclude that younger age of onset, male sex, high titers of ICA, severe clinical presentation, and shorter symptom duration significantly predict accelerated rates of loss of C-peptide secretion.

Age Factors↗

Growth hormone response in very short children.

Growth hormone (GH) response to standardized exercise, L-DOPA/propranolol and a 6-h diurnal GH profile (GHP) were evaluated in twenty-three children with very short stature and abnormal growth velocities. Standardized exercise (Jones Stage I) was performed on a cycle ergometer at 53% of the maximum oxygen consumption (VO2max) for 20 min. VO2max was determined by an incremental progressive workload until exhaustion. The mean +/- SEM peak GH concentration (ng/ml) for each test was: exercise, 8.7 +/- 1.3; L-DOPA/P: 12.8 +/- 1.9 and GHP: 3 +/- 0.7. There was no statistical difference between exercise and L-DOPA/P peaks but both peaks were significantly higher than the peak observed during the profile. During exercise 14 of 23 patients had a GH response greater than 8 ng/ml. Two patients were found to be GH deficient. Therefore 16 of 23 patients (86%) had a result concordant with their final diagnosis. During the L-DOPA/P test 17 of 23 patients had a GH response greater than 8 ng/ml. By contrast only 6 of 23 patients had a positive response during GHP. Standardized exercise is as effective as L-DOPA/P as a stimulation test for growth hormone response in very short children with abnormal growth velocities. Exercise has the advantages of being physiological, having minimal side effects, and requiring fewer blood samples. In this population of children, exercise and L-DOPA/propranolol are significantly better than the 6-h growth hormone profile for assessing GH secretion.

Adolescent↗

Cluster analysis of an insulin-dependent diabetic cohort towards the definition of clinical subtypes.

Clinical and biochemical data on 111 consecutive insulin-dependent diabetic children enrolled in a longitudinal prospective study were analyzed to determine if more than one clinical expression of Type I diabetes exists. Use of multivariate statistical methods, including Correspondence Analysis, kappa-means clustering and RECPAM (RECursive Partition and AMalgamation), show that there are two well differentiated clinical expressions of IDDM each characterized by a cluster. One is characterized by later age, less severe onset, longer symptom duration, less beta-cell disappearance after 12 months, more females; the other by earlier age, more sudden and severe onset, DR 3/4, earlier disappearance of beta-cell function and more males. RECPAM analysis provides further insight into the structure of the two clusters. An other RECPAM tree identifies low, medium and high risk groups of disappearance of beta-cell function at 12 months after diagnosis.

Adolescent↗

Two-color flow cytometry analysis of activated T-lymphocyte subsets in type I diabetes mellitus.

We addressed the question of whether newly diagnosed type I (insulin-dependent) diabetes mellitus patients showed an increased number of DR (la+) T-lymphocytes compared with nondiabetic siblings and normal control subjects. Two-color flow cytometry measurements of peripheral-blood lymphocytes showed a slight but statistically significant increase in DR+ T-lymphocytes in diabetic subjects as well as the nondiabetic sibling control compared with the normal control subjects. This difference was not present in long-term-diabetic subjects. Thus, in addition to minor changes in this lymphocyte subset in peripheral blood, the sibling data demonstrate a lack of specificity for the disease; therefore, these measurements are probably of limited diagnostic usefulness.

Adolescent↗

Prospective study of predictors of beta-cell survival in type I diabetes.

We conducted a prospective study to describe the course of the pancreatic beta-cell function from the time of clinical diagnosis of insulin-dependent (type I) diabetes to determine whether DR type, presence of islet cell antibodies (ICA), presence of insulin antibodies (IA), age at onset, and sex could help in the prediction of residual endogenous insulin secretion. A cohort of 68 children was followed for 18 mo after diagnosis of type I diabetes. The outcome variables selected for analysis were 1) serum C-peptide peak concentration after a Sustacal meal, 2) time of disappearance of the serum C-peptide response, and 3) time after diagnosis at which the maximal serum C-peptide response was observed. After institution of insulin therapy, serum C-peptide peak concentrations rose temporarily for 1-6 mo and declined thereafter. Multivariate analysis of the data showed that DR type (P = .2488) and presence of IA (P = .1604) had no effect on serum C-peptide over time, but sex (P = .0146), age at onset (P = .0002), and presence of ICA (P = .0147) significantly contributed to the variation of serum C-peptide over time. Furthermore, age at onset, presence of ICA, and sex were also the only significant predictors of the time of disappearance of the beta-cell function. The relative risks of beta-cell-function disappearance were 0.87 (P = .0015), 9.43 (P = .0181), and 2.25 (P = .0468), respectively. In conclusion, there are distinct variations in the natural course of the beta-cell function in type I diabetes. beta-Cell-function survival is significantly shortened the younger the subject is at disease onset, if ICA are present at diagnosis, and if the subject is male.

Adolescent↗