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A Schiffrin

Publications and source records attributed to A Schiffrin.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

The risk of developing disease for siblings of patients with insulin dependent diabetes mellitus.

We analyzed the risk of developing insulin-dependent diabetes mellitus (IDDM) in 411 siblings of patients with IDDM. We found that siblings who had a positive test for antibodies against islet cells (ICA) at the time of diagnosis of the index case had a higher risk of developing IDDM than did those who had negative tests. However, of the ten siblings who developed IDDM, only four were positive at the initial testing. The period of time elapsing from a negative test at screening to a positive test at diagnosis varied but was less than one year in one child. Two of the ten siblings who developed IDDM had negative tests both at screening and at diagnosis. Amongst siblings who were negative at the initial screening, those in whom the index case was diagnosed at a young age had a higher risk of developing IDDM than did those in whom the index case was diagnosed at an older age. The age of the sibling at the time of screening, the sex of the sibling, and a positive family history (one which includes in addition to the index case one or more first-degree relatives with IDDM) did not confer increased risk. Our data suggest that screening for ICA will have to be done often and will have to be continued into adult life in order to identify the 70-80% of diabetics who will be positive at some time in the evolution of their disease.

Adolescent↗
PubMed1990

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↗
PubMed1989

Severe hypoglycemia in IDDM children.

The incidence of severe hypoglycemia was determined in a 1-yr prospective study of 350 insulin-dependent diabetic (IDDM) children. There were no significant differences in mean glycosylated hemoglobin, age, and duration of disease between the patients who had severe hypoglycemia and those who did not. There were 25 episodes in 24 patients (6.8%). Their insulin doses at the time of the episode (U.kg-1.day-1) were significantly higher than those of the nonhypoglycemic group (mean +/- SD 1.01 +/- 0.30 vs. 0.89 +/- 0.29; P = .04). The hypoglycemic group had a significantly higher mean number of previous episodes of severe hypoglycemia than the nonhypoglycemic group (0.92 +/- 1.18 vs. 0.25 +/- 0.68; P = .01). In only 64% of the episodes, an unusual circumstance such as strenuous physical activity or missed or delayed meals preceded the event. Multivariate analysis of the data by logistic regression showed risks of developing hypoglycemia of 2.5 per 0.5 U/day insulin and of 2.0 per previous episode of severe hypoglycemia. We conclude that severe hypoglycemia may be a recurrent problem in some diabetic children, but it does not appear to be related to age or blood glucose control. The presence of previous episodes may be a guide to identify patients at greater risk of developing severe hypoglycemia. Adherence to regular testing, strict spacing and consistency of meals, and extra food for extra activity may reduce this serious complication.

Child↗
PubMed1988

Kenny syndrome: description of additional abnormalities and molecular studies.

An 18-month-old girl presented with clinical manifestations of Kenny syndrome including growth retardation, ophthalmologic abnormalities, a persistent open anterior fontanel, dysmorphic facies, anemia, radiologic skeletal abnormalities, and severe hypoparathyroidism. Analysis of restriction patterns of DNA with human parathyroid hormone (PTH) DNA probes revealed no gross abnormalities of the PTH gene that could contribute to the hypoparathyroidism. In addition to the previously described characteristics of the syndrome, hypoplastic nails, persistent neutropenia, abnormal T cell function and neonatal liver disease all occurred and may be additional manifestations of Kenny syndrome, requiring diagnostic or therapeutic consideration.

Abnormalities, Multiple↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

Hyperglycemia after intense exercise in IDDM subjects during continuous subcutaneous insulin infusion.

Exercise is conventionally considered a modality for improvement of glycemia in diabetes. We have found that a short period of intense exercise (80% VO2max) in normal lean subjects produces sustained postexercise hyperglycemia 20% above basal with a corresponding 100% increase in plasma insulin. In people with insulin-dependent diabetes mellitus (IDDM) incapable of this insulin response, it was predicted that postexercise hyperglycemia would be of greater magnitude and/or duration. To investigate this possibility, the effects of the same intense exercise (80% VO2max) were studied in 8 IDDM subjects (2 on 2 occasions) in the postabsorptive state with continuous subcutaneous (abdominal) insulin infusion (CSII). When the preexercise plasma glucose was normal (n = 6, 86 +/- 4 mg/dl), there ensued a postexercise hyperglycemia to 127 +/- 7 mg/dl (P less than .001) sustained for 2 h postexhaustion. Plasma free immunoreactive insulin (IRI) was 1.43 +/- 0.12 ng/ml before exercise and did not change postexercise. When mean preexercise plasma glucose was 149 +/- 9 mg/dl (n = 4), it rose progressively throughout the 2 h of recovery to 229 +/- 28 mg/dl (P less than .025). A small but statistically significant decrease in free IRI occurred during the last 80 min of recovery. Hyperglycemia in the diabetic subjects was not explained by abnormal or differing responses of glucagon or catecholamines. Thus, with intense exercise, diabetic control deteriorates rather than improves. Therefore, different therapeutic strategies may be required for intense compared with moderate exercise in IDDM patients.

3-Hydroxybutyric Acid↗
PubMed1988

Impact of SMBG on control of diabetes as measured by HbA1. 3-yr survey of a juvenile IDDM clinic.

Three hundred twelve diabetic children and adolescents were seen in our diabetic clinic and instructed to test their capillary blood glucose (CBG) twice daily and to use an algorithm to adjust their short-acting insulin. Of this group, 219 youngsters had a full 3-yr period of observation. At each clinic visit, blood was obtained for fasting blood glucose and HbA1 and, once a year, cholesterol and triglycerides were also measured. Patient and parent accuracy in measuring CBG was found to be adequate. The changes over time in HbA1 were nondifferential across age and sex, and there was no difference in the level of HbA1 between age and sex groups, the number of tests reported to have been done by the patients, the number of injections of insulin per day, or the serum cholesterol. There was a significant relationship between the HbA1 and the fasting blood glucose (P less than .001) measured by the laboratory as well as with the serum triglyceride (P less than .01). The failure to improve diabetic control, despite measures that would have been expected to do so, was believed to relate more to a lack of compliance than to a flaw in the therapeutic approach. It was interesting to note that the adolescent patients in the study were in no worse control than the younger children in the group. Although better technical skills are available today to manage diabetes, the psychosocial approach to patient motivation requires improvement.

Adolescent↗
PubMed1987

Predicting nocturnal hypoglycemia in patients with type I diabetes treated with continuous subcutaneous insulin infusion.

The incidence of low nocturnal blood glucose values (i.e., less than 65 mg/dl) was assessed in 20 insulin-dependent diabetic patients treated with continuous subcutaneous insulin infusion supported by capillary blood glucose monitoring before each meal and the evening snack. Patients were randomly assigned to a control or experimental group. Both groups followed an identical protocol for the first part of the study (baseline). Patients were instructed to determine capillary blood glucose measurements five times during the night for three consecutive nights. The same procedure was repeated one week later, but this time the subjects in the experimental group were instructed to have an extra snack if capillary blood glucose levels at 10:30 P.M. were 120 mg/dl or less. The control group continued with the usual routine of one evening snack at 9 P.M. At baseline, the incidence of capillary blood glucose values of less than 65 mg/dl was 13 percent. The ingestion of an extra snack at bedtime resulted in the absence of capillary blood glucose values of less than 65 mg/dl in the experimental group, whereas the incidence of capillary blood glucose values of less than 65 mg/dl in the control group remained 13 percent (p = 0.038). The capillary blood glucose concentration at 10:30 P.M. was highly predictive of the risk of nocturnal blood glucose values below 65 mg/dl (p = 0.015) and fasting capillary blood glucose values above 140 mg/dl (p = 0.0001). These data show that nocturnal hypoglycemia may be a considerable problem during continuous subcutaneous insulin infusion therapy even if the basal infusion rate is adjusted in the hospital on the basis of nocturnal blood glucose concentrations. The ingestion of an extra snack at bedtime for capillary blood glucose values below 120 mg/dl has the potential to minimize this risk. The capillary blood glucose concentration at 10:30 P.M. is a significant predictor of nocturnal hypoglycemia.

Adolescent↗
PubMed1986

An autosomal dominant form of adolescent multinodular goiter.

Eighteen members of an extended pedigree have been found to have a form of euthyroid adolescent multinodular goiter. Histological examination showed multiple adenomata with areas of epithelial hyperplasia, hemorrhage, and calcification. In two subjects there were focal areas of epithelial hyperplasia reminiscent of low-grade papillary carcinoma, but capsular and vascular invasion was not found. The pattern of inheritance appeared to be autosomal dominant, with diminished penetrance in males. Although the patients were euthyroid, the likely basis for this disorder is an abnormality in thyroglobulin structure and function.

Adolescent↗
PubMed1979

Partial short arm deletions of the X chromosome and spontaneous pubertal development in girls with short stature.

Five additional examples of partial deletion of the short arm of the X chromosome are reported. All of the patients had short stature. The presence of the other stigmata of Turner syndrome, including ovarian dysfunction, appeared to depend on the location of the deletion. Chromosomal analysis of girls with short stature (less than 140 cm), normal pubertal development, and regular menses may reveal that minor deletions of the short arm of the X chromosome are more frequent than has been previously reported.

Adolescent↗
PubMed1978

Increased plasma somatomedin reactivity in chronic renal failure as determined by acid gel filtration and radioreceptor assay.

Plasma Somatomedin (SM) reactivity has been determined in patients with chronic renal failure and in normal children by radioreceptor assay (RRA) following acid gel filtration on Sephadex G-100. Total small molecular weight SM reactivity was obtained by the summation of all values between Kav 0.55 to 0.75. The mean SM reactivity (+/-SE) for the renal failure group (N = 9) was 154 +/- 10 ng/ml and for the normal subjects (N = 9) was 91 +/- 5 ng/ml (p less than .001). The renal failure group also had significantly increased mean levels of insulin, GH and PRL, but individual increases were not always concordant. Our data reveal that small molecular weight SM reactivity as determined by RRA of column eluates is increased in chronic renal failure compared to normal controls. Thus SM reactivity is not low in chronic renal failure, supporting the suggestion that peripheral antagonism to SM action contributes to the growth failure observed in these patients.

Adolescent↗