PubMed Health⌕ Search

Biomedical subjects

D Daneman

Publications and source records attributed to D Daneman.

At least 37 records · Page 2Linked to original sources
PubMed1989

Severe hypoglycemia in children with insulin-dependent diabetes mellitus: frequency and predisposing factors.

We surveyed 311 children with insulin-dependent diabetes mellitus to evaluate the frequency and characteristics of those children experiencing severe hypoglycemia (defined by an episode of coma, convulsion, or both). The children and their parents completed a questionnaire, and we reviewed the hospital records to confirm reported episodes. Ninety-seven (31%) reported severe hypoglycemia, and a further 50 (16%) reported moderate hypoglycemia requiring the assistance of another person but not resulting in coma or convulsion. In 164 children (53%) there was no history of either moderate or severe hypoglycemia. Sixty-nine (22%) reported the occurrence of more than one severe hypoglycemic episode (range 2 to 20); 52 (16%) reported such an event in a single year. A total of 285 episodes were reported, 39% during sleep and 61% while awake. Children reporting such events tended to have diabetes of longer duration and be younger at the time of the first episode. Hemoglobin A1c concentration at the time closest to the severe episode was significantly lower than in children reporting no hypoglycemia. All families had been taught to use glucagon to reverse severe hypoglycemia at home, but it was available in only 80 of the 97 homes and used in only 30. These data suggest that severe hypoglycemia is common in children with insulin-dependent diabetes mellitus who are treated conventionally. Greater vigilance and education are required both to prevent and to treat severe hypoglycemia in children with insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1989

Relationship of insulin autoantibodies to presentation and early course of IDDM in children.

Insulin antibodies have been documented before (insulin autoantibodies [IAAs]) and after (insulin antibodies) insulin administration in children with new-onset insulin-dependent diabetes mellitus (IDDM). Whereas the relationship of IAA to various factors at presentation has been studied in some detail, little is known about their relationship to events during the 1st yr after diagnosis. Furthermore, the course and factors affecting insulin-antibody response to human insulin administration in children with newly diagnosed IDDM remain poorly defined. To study these questions, we measured serum glucose, pH, bicarbonate, C-peptide, and IAA at diagnosis in 84 children between 0.5 and 18 yr of age. Basal and peak C-peptide responses to Sustacal ingestion, glycosylated hemoglobin (HbA1c), and IAA were then measured in 33 of these patients at 10 days and 1, 3, 6, and 12 mo after diagnosis. At presentation, IAAs were absent (binding below the mean + 3SD of the binding of control serums) in 51 patients (61%) and present (binding above the mean + 3SD) in 33 patients (39%). Multiple regression analysis showed a significant nonlinear relationship between IAAs and both age (P less than .005) and blood glucose (P less than .05) at onset. There was a stepwise increase in median insulin-antibody binding throughout the 1st yr. This increase was most marked during the 1st mo of insulin therapy and showed a statistically significant difference between successive measurements only during this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Relationship of islet cell and islet cell surface antibodies to the presentation and early course of IDDM in childhood.

Islet cell (ICA) and islet cell surface (ICSA) antibodies were measured in 30 children (aged 6-17.7 years) with newly diagnosed insulin-dependent diabetes mellitus (IDDM) to determine the relationship of antibody positivity/negativity to a variety of factors both at presentation (e.g., age, severity of onset, residual insulin secretion, insulin autoantibodies) and during the first year thereafter (HbA1c, insulin antibody binding, residual insulin secretion). At diagnosis, 10 of 30 were ICA (+) and 13 ICSA (+): no differences were found between ICA (+) and (-) subjects at onset; however ICSA (+) children had a lower bicarbonate concentration than those (-) for ICSA (P less than 0.01). During the first year after diagnosis the only significant finding was that in ICA (+) patients insulin dose (units/kg) was lower at both 6 and 12 months (mean +/- SD 0.55 +/- 0.14 and 0.67 +/- 0.12 U/kg, respectively) than ICA (-)'s (0.70 +/- 0.22 and 0.96 +/- 0.38, respectively, both P less than 0.05). Those children positive for both ICA and ICSA did not differ in any way at onset or during the subsequent 12 months from those negative for both antibodies. These results suggest that, except for minor differences, the presentation and course during the first year after diagnosis of IDDM do not differ in those children positive or negative for either or both ICA and ICSA.

Adolescent↗
PubMed1988

Thyroid scanning, ultrasound, and serum thyroglobulin in determining the origin of congenital hypothyroidism.

Congenital hypothyroidism (CH) can be due to an absent gland (athyrosis), an ectopic gland (usually lingual), or an inborn metabolic error (goiter). In this study, radionuclide scanning was compared with ultrasound (US) and serum thyroglobulin (Tg) concentration as a method of determining the cause of CH in 50 newborns. Mean serum Tg values were significantly lower in athyrotic children (7.9 pmol/L) than in either those with goitrous (149.1 pmol/L) or ectopic (60.5 pmol/L) glands, but there was marked overlap among all three groups. With the interpreter "blinded" to the radionuclide diagnosis, a cervical gland could be delineated reliably on US. All 12 goiters and five of five normal glands were identified. In contrast, the correlation between US and radionuclide scanning was poor in patients in whom there was no cervical thyroid tissue. Ultrasound failed to identify 13 lingual glands and was reported as normal in four of 12 children with no radionuclide uptake in the neck and biochemical hypothyroidism. Two children with absent thyroid glands on scanning were biochemically euthyroid. The serum of two others who had normal results of radionuclide studies showed persistent hypothyroidism. Thyroid scanning remains the most accurate diagnostic modality to determine the cause of CH. Serum Tg and cervical US have not been established as reliable alternatives.

Choristoma↗
PubMed1988

Evidence for a critical role of diet in the development of insulin-dependent diabetes mellitus.

The role of diet in human insulin-dependent diabetes mellitus (IDDM) has not been properly examined, mainly due to a lack of reliable markers to identify prospective diabetics and the difficulties in obtaining accurate and representative dietary information. Nonetheless, there is some circumstantial evidence suggesting a role for diet in human IDDM. The validity of this relationship in humans must await a sufficiently large, well designed prospective study or the discovery of better markers for diabetes predisposition. The recent availability of the spontaneously diabetic BB rat has permitted prospective studies under controlled conditions which indicate diet, particularly dietary proteins, such as wheat gluten or cow's milk proteins may be prerequisites for maximum expression of the insulin-dependent syndrome in these animals. The early suckling and/or post-weaning period appears to be important and may be the crucial time when these proteins or portions of them pass the gastrointestinal barrier and initiate a process, possibly immunological, which results in destruction of the beta cells of the pancreas.

Animals↗
PubMed1987

Factors affecting and patterns of residual insulin secretion during the first year of type 1 (insulin-dependent) diabetes mellitus in children.

We measured serum C-peptide, glucose, pH, islet antibodies and insulin antibody binding at diagnosis in 84 children with Type 1 (insulin-dependent) diabetes. In a subgroup of 33 children, residual insulin secretion (basal and peak C-peptide response to Sustacal), insulin antibody binding and HbA1c were measured at 10 days, 1, 3, 6 and 12 months. At presentation C-peptide correlated positively with age at onset and negatively with the blood glucose concentration. Median C-peptide concentration at diagnosis was low, rose significantly (p less than 0.05) at 10 days, reached a maximum at 1-3 months and declined gradually to 1 year. C-peptide concentration both at diagnosis and at 10 days correlated with that at 3 and 6 months. Of the factors investigated, only age (p less than 0.005) and sex (higher in females, p less than 0.01) were found to have a significant influence on basal/peak C-peptide levels throughout the first year. In particular there was no relationship between C-peptide, HbA1c and insulin dose during this period. A peak C-peptide response at 3-6 months greater than/less than 0.32 nmol/l was used to divide the group into two: 16 had a peak response less than 0.32 nmol/l (low secretors) while in 17, the peak C-peptide was greater than 0.32 nmol/l (high secretors). While the low secretors had significantly (p less than 0.05) lower C-peptide levels during the first year, there were no differences between low and high secretors in HbA1c or insulin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Factors affecting insulin antibody binding in children with insulin-dependent diabetes mellitus.

We measured insulin antibody binding in 2 groups of patients: Study 1, 32 children with newly diagnosed IDDM before onset of insulin therapy, and, in 20 of these, 10 days, 1, 3, and 6 months after beginning therapy; and Study 2, 35 children with long-standing IDDM, 20 of whom had free insulin concentrations measured before, and for 2 hours following subcutaneous injection of 0.25 U/kg regular insulin. Almost 35% of new onset subjects had insulin antibody binding above control levels. In those studied prospectively, binding increased significantly with time. Pre-treatment binding did not correlate with later insulin antibody binding nor metabolic control. In Study 1 we have confirmed previous studies showing abnormally high insulin antibody binding in children with IDDM pre-treatment. We have been unable to demonstrate a relationship between this binding and that found 6 months after initiation of therapy. In Study 2, we have shown that insulin antibody binding is not related to either the level of metabolic control or the rate of rise of free insulin levels in children with IDDM.

Adolescent↗
PubMed1987

Residual beta-cell function in children with type 1 diabetes: measurement and impact on glycemic control.

We studied residual beta-cell function in 84 children with IDDM to assess (1) relationship between basal and stimulated C-peptide concentrations; (2) reproducibility of testing (Group 1, n = 20); (3) the effect of exogenous insulin on test interpretation (Group II, n = 20); and (4) impact on metabolic control. Sustacal (a mixed liquid meal) was utilized as the test stimulus. In C-peptide positive subjects (n = 44) there was a strong correlation between basal and peak C-peptide concentrations (r = 0.88, p less than 0.001). In Group 1 subjects, Sustacal proved to be a highly reproducible test stimulus producing identical results on two tests 7-14 days apart. The results of the tests were not affected by the administration of subcutaneous regular insulin prior to the second test in Group II. Peak C-peptide correlated inversely with HbA1, insulin dose, and disease duration (r = -0.29, -0.40, and -0.33 respectively, p less than 0.05) and positively with age (r = 0.34, p less than 0.05). We conclude that Sustacal is a highly reproducible stimulus to residual beta-cell function in IDDM and is not affected by exogenous insulin. This residual insulin secretion has a small but significant effect on glycemic control.

Adolescent↗
PubMed1987

Dietary triggers of insulin-dependent diabetes in the BB rat.

Environmental "triggers" (including viruses, toxins and dietary factors) have been implicated in the pathogenesis of insulin-dependent diabetes mellitus. Data have suggested a possible role for cow's milk protein (CMP) as a trigger of diabetes. To study this further, 86 BB rats were divided into 2 groups during the weaning period (days 13-25): Group A received rat chow without CMP; Group B, rat chow with 1% CMP added. Each group was subdivided afterwards into 2: Groups A1 and B1 received chow without CMP; Groups A2 and B2, chow with CMP. Animals weaned with chow containing CMP (B1 and B2) had a higher incidence of diabetes (66%) than those weaned without (A1 and A2; 29%, p less than 0.001). The incidence in both B1 and B2 was significantly greater than in either A1 or A2 (p less than 0.05). The highest incidence of diabetes occurred in male rats weaned on rat chow with CMP (90%), the incidence being significantly higher than female rats weaned with (43%) or without CMP (18%) and males weaned without CMP (39%). Thus, it appears that (a) the presence of cow's milk protein in the diet increases the incidence of diabetes in the BB rat; (b) the critical time for exposure to CMP appears to be the weaning period; and (c) male rats appear to be more susceptible to the development of diabetes than female rats, when exposed to this trigger. This supports the hypothesis that dietary triggers may play an important role in the expression of diabetes in the susceptible host and that its prevalent action occurs early in life.

Animals↗
PubMed1986

Subclinical diabetes mellitus in the BB rat.

The spontaneously diabetic BB Wistar rat is a well recognized animal model for the study of insulin-dependent diabetes mellitus (IDDM). Previously we have noted hyperglycemia and insulitis in BB rats without clinical diabetes. 121 rats were studied prospectively. 43 (36%) were normal and 64 (52%) developed IDDM suspected by the presence of glycosuria and acute weight loss, and confirmed with pancreatic histology. In the remaining 14 (12%) animals, pancreatic histology was also abnormal, varying from mild insulitis only to moderate insulitis and beta-cell degranulation. Since these rats gained weight normally, had no glycosuria, or hyperglycemia they were designated as having subclinical diabetes. At death, their plasma-insulin concentrations and the amount of extracted pancreatic insulin was intermediate between that of the normal and diabetic group (p less than 0.001). We have identified a group of rats with pancreatic features of diabetes but no clinical expression. Further investigation of this syndrome may reveal clinical, immunological or histological features which protect these animals from the development of overt disease.

Animals↗
PubMed1986

Amiodarone therapy effects on childhood thyroid function.

Thyroid function was systematically evaluated in 15 consecutive children (mean age 13.7 years, range 0.5 to 19.5 years) before and serially during treatment with amiodarone (Cordarone), a potent antiarrhythmic agent. Amiodarone is known to affect thyroid homeostasis by competitive inhibition of 5'-monodeiodinase, which converts L-thyroxine (T4) to triiodothyronine (T3) and reverse T3 (rT3) to 3,3'-diodothyronine (T2), and also by the direct effects of its high iodine content (37% by weight). Clinical and/or biochemical evidence of hypothyroidism occurred in three patients, two of whom required treatment with L-thyroxine. An additional patient had persistent hyperthyroxinemia but no clinical evidence of hyperthyroidism. Results from the patients who remained euthyroid showed characteristic alterations in serum thyroid function tests. These included significant increases in serum T4, rT3, basal thyroid-stimulating hormone and thyroid-stimulating hormone response to thyrotropin-releasing hormone testing. These changes were considered to be compensatory adjustments by the pituitary-thyroid axis to competitive inhibition of 5'-monodeiodinase by the amiodarone. Routine screening of thyroid function is needed to allow early detection of hypothyroidism when these compensations fail to occur.

Adolescent↗
PubMed1985

Congenital hypothyroidism. The effect of stopping treatment at 3 years of age.

Fifty-six children with congenital hypothyroidism diagnosed by neonatal screening were reviewed at 3 years of age or older. The presence or absence of the thyroid gland was determined by radionuclide scanning prior to treatment in the newborn period. Thyroxine therapy was discontinued in those children who did not have anatomic defects or a secondary rise in their thyrotropin (thyroid-stimulating hormone [TSH]) level once it was suppressed by thyroid hormones. Sixteen of 17 children developed a low thyroxine and an elevated TSH level within three to six weeks. One child was not receiving thyroxine for nine months and was clinically and biochemically euthyroid. We conclude that (1) newborn thyroid scans are useful to determine the cause of hypothyroidism, (2) a secondary rise in the TSH level indicates permanent hypothyroidism, (3) only about one third of infants whose condition is diagnosed by newborn screening will qualify for a trial off therapy at 3 years of age, (4) only 1% to 2% of infants whose condition is diagnosed by newborn screening have transient hypothyroidism, and (5) a three-week period of hormone withdrawal after the age of 3 years seems adequate and safe to confirm permanent hypothyroidism.

Child, Preschool↗
PubMed1985

Anorexia nervosa and bulimia in female adolescents with insulin dependent diabetes mellitus: a systematic study.

An unselected sample of 46 female adolescents with insulin-dependent diabetes mellitus (IDDM) for more than one year were assessed systematically for the presence of anorexia nervosa and bulimia. These disorders and their partial syndromes were found in 19.5% of this population. Anorexia nervosa and bulimia diagnosed on the basis of DSM-III criteria were each found in 6.5% of the population representing approximately a 6-fold and 2-fold increase respectively in the expected prevalence for similar nondiabetic individuals. Bulimic symptoms were associated with poor metabolic control as reflected in blood levels of glycosylated hemoglobin (HbAl). These findings have important implications both for the pathogenesis of anorexia nervosa and bulimia and for the management of some cases of IDDM with unstable metabolic control.

Adolescent↗
PubMed1985

The relationship of metabolic control to growth and pubertal development in children with insulin-dependent diabetes.

Growth and pubertal development were studied in 122 children aged 13.4 +/- 2.9 yr (mean +/- SD) with IDDM of 6.1 +/- 3.8 yr duration. Height and weight, pubertal status, insulin dose (u/kg), frequency of insulin administration and HbA1 were measured every 3 months for a minimum period of 1 yr for each child. The mean and distribution of height and height velocity percentiles were normal for boys and girls. The mean weight percentile for boys was increased (62 +/- 27, p less than 0.01), but was normal for girls. The mean and distribution of weight velocity percentiles were normal for both sexes. The mean and distribution of age of onset of Tanner 2 in both boys (11.9 +/- 1.4 yr) and girls (11.2 +/- 1.3) was normal, as was the age of menarche (13.2 +/- 1.2 yr). The mean HbA1 level was 11.1 +/- 2.0% (normal less than 7.5%). There was no correlation of mean HbA1 levels (calculated from 4 or more measurements for each child) with height velocity or with weight velocity percentiles or with mean height or weight percentiles. These results indicate that diabetic control, as reflected by HbA1 levels, was not a major determinant of growth in this group of children with IDDM, who displayed normal growth patterns and pubertal development despite a wide range of HbA1 levels. Normal growth may not reflect optimal metabolic control but "average" control.

Adolescent↗