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Biomedical subjects

D Daneman

Publications and source records attributed to D Daneman.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1984

The "empty sella" in childhood.

The "empty sella" (ES), a common entity in adults, is so named because a cerebrospinal fluid-filled arachnoid hernia fills the pituitary fossa and compresses the pituitary gland, creating the illusion of an "empty" sella. We report our experience of ES in childhood. Our four cases represent associations with ES that have not been previously described in childhood: case 1 was associated with central precocious puberty; case 2 with secondary ES resulting from shrinkage of a prolactinoma during bromocriptine therapy; case 3 with pseudotumor cerebri; and case 4 with no significant pathology. Together, they account for approximately 1 percent of cases of radiographically enlarged sella tursica investigated here. This brings the number of cases of ES reported in children to 27. Review of these 27 cases reveals seven with local skull dysplasia and/or a familial inheritance. The remainder lacked clinical homogeneity or similarity to the common adult variety of ES. Children with ES did not exhibit the higher female preponderance reported in adults with ES. They showed a higher frequency of secondary cases (4/27), and of associated endocrine (10/15) and visual (8/17) abnormalities than is seen in adults with the "empty sella."

Adolescent↗
PubMed1984

An automated "high-pressure" liquid-chromatographic assay for hemoglobin A1c.

An automated "high-pressure" liquid-chromatographic assay for hemoglobin A1c is described. We use a 45-min incubation in acetate buffer (pH 5.5) to eliminate labile glycated hemoglobins. In this automated system conventional modules are used but it incorporates a solvent-switching valve to select either of two buffers, which differ in pH and NaCl concentration. The chromatographic column contains "polyCAT" (a weak cation-exchanger, polyaspartic acid linked to silica). Run time is 14 min per sample. The method is precise and results correlate well with those by other ion-exchange procedures.

Adolescent↗
PubMed1983

Gender assignment in male pseudohermaphrodite children.

Experience with male pseudohermaphrodites at The Hospital for Sick Children, Toronto, from 1976 to 1981 was reviewed to identify factors that had influenced gender assignment. Seventeen children with microphallus, ambiguous genitalia, and 46 XY karoytype were studied. Five had been raised as females and 12 as males. Of those raised as females, 3 were from families with prior experience of androgen insensitivity. The other 2 had gross perineal abnormalities in addition to genital ambiguity. Of those raised as males 6 were not considered for gender reassignment, 4 because they were too old at presentation, and the other 2 because of parental refusal. In this series the parents were not prepared to accept gender reassignment on the basis of a small phallus alone. Androgen stimulation so far has been a reliable indicator of phallic growth potential, but long-term follow-up is necessary to determine its true value.

Adolescent↗
PubMed1983

Proteinuria in children with insulin-dependent diabetes: relationship to duration of disease, metabolic control, and retinal changes.

The relationship of early retinal changes and subclinical proteinuria to duration and metabolic regulation of insulin-dependent diabetes was studied in 67 children. Retinopathy was found in 25 patients and occurred almost exclusively (96%) in those with duration of disease longer than five years. Glomerular filtration rate was normal or increased in all patients. Urinary excretion of beta 2-microglobulin, albumin, transferrin, and IgG was significantly increased in patients, as compared with controls, whereas serum concentrations of these proteins were generally normal. The mechanisms responsible for the hyperexcretion of both large and small proteins are unclear but probably involve both glomerular and tubular dysfunction. Increased urinary protein excretion occurred independently of duration of disease. Retinopathy but not microproteinuria was more common in patients with glycosylated hemoglobin greater than 11% and in those with duration of disease longer than five years. Although a significant association was found between retinopathy and the hyperexcretion of one or more of the large molecular weight proteins, the weight of the evidence suggests that these two sequelae of diabetes differ in their pathogenesis. Long-term follow-up of these patients may provide insight as to their risk of developing more serious retinopathy or nephropathy, and whether good glycemic control may protect against these complications of insulin-dependent diabetes.

Adolescent↗
PubMed1983

Use of ultrasound in childhood thyroid disorders.

Thyroid ultrasound findings in 55 patients aged 6 days to 19 years were reviewed to assess the importance of this technique in evaluating childhood thyroid disorders. Findings were correlated with the available clinical, radionuclide, and pathologic data. In 25 patients with diffuse thyroid lesions (thyroiditis, Graves disease, euthyroid goiter, iodine-induced goiter, goitrous cretinism), ultrasound revealed only homogeneous thyroid enlargement or a nonspecific patchy echo pattern. In two infants with poorly visualized glands on radionuclide scans, ultrasound confirmed the presence of anatomically normal thyroid tissue. Twenty patients had at least one focal thyroid lesion seen by ultrasound, including nodules not detected by palpation in one child or by technetium scan in three. Thyroid malignancies were found in four of 13 patients with solitary thyroid nodules, occurring in two of four patients with echogenic nodules, two of five children with complex lesions, and none of four with echofree nodules. Thyroid ultrasound is a sensitive, noninvasive means of evaluating thyroid anatomy. Because it can detect thyroid tissue in the neck not seen on radionuclide scan in patients at all ages and can define the number and consistency of focal lesions, this technique offers definite advantages in assessing a variety of childhood thyroid disorders.

Adolescent↗
PubMed1982

Diurnal glucose--dependent fluctuations in glycosylated hemoglobin levels in insulin-dependent diabetes.

In order to evaluate the relationship between short-term glycemic control and the stable and labile fractions of GHb, we performed hourly blood glucose samplings for 24 hr on 31 occasions in 13 children with IDDM of varying duration. GHb was measured both in hemolysates of whole blood and after 48 hr incubation at 4 degrees C in normal saline to remove the labile fraction of GHb. SI-GHb was always lower than WB-GHb (p less than 0.0001). MGB correlates closely with WB-GHb (r = 0.58, p less than 0.001) and less closely with SI-GHb (r = 0.45, p less than 0.05). The daily fluctuations in SI-GHb were always significantly less than in WB-GHb (p less than 0.005). The labile fraction correlated closely with MAGE (r = 0.62, p less than 0.0001). In one subject WB-GHb decreased by 4.4% and SI-GHb by 3.1% over a 7 wk period of good glycemic control. These results (1) confirm the presence of the stable and liable forms of GHb; (2) a closer correlation of short-term control with WB-then SI-GHb; and (3) highlight the possible relationship of the labile fraction of GHb to diabetic instability as assessed by MAGE.

Adolescent↗