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Biomedical subjects

Denis Daneman

Publications and source records attributed to Denis Daneman.

At least 37 records · Page 2Linked to original sources
PubMed2004

Continuous subcutaneous insulin infusion pump treatment in children with type 1 diabetes mellitus.

Data were reviewed from 73 consecutive medical charts of children and adolescents with type 1 diabetes mellitus using insulin pumps for more than 6 months at The Hospital for Sick Children, Toronto, Canada. Statistically significant differences in HbA1c (-0.8%), body mass index (+1.45 kg/m2) and total daily dose of insulin (-0.23 U/kg/day) were found between the start of pump use and evaluation 6-30 months later. There was a close correlation between the HbA1c before and after 6-30 months of pump therapy.

Adolescent↗
PubMed2004

Potential adjunctive therapies in adolescents with type 1 diabetes mellitus.

Appropriate insulin therapy is central to the management of all individuals with type 1 diabetes mellitus. The potential role of adjunctive therapy in type 1 diabetes is to improve insulin action, and facilitate the ability of all individuals with type 1 diabetes to achieve and maintain 'better' metabolic control. The landmark clinical trial in type 1 diabetes is the Diabetes Control and Complications Trial (DCCT). The DCCT showed that there is no threshold below which a reduction in glycemia would not provide further benefit against diabetes-related microvascular complications. This study in particular provides the rationale for attempting to achieve as near normoglycemia as possible. We review the use of recognized pharmacologic agents as potential insulin adjunctives in children and adolescents with type 1 diabetes. Adjunctive therapies can be grouped into the following categories based on their putative mechanism of action: enhancement of insulin action (e.g. the biguanides and thiazolidinediones), alteration of gastrointestinal nutrient delivery (e.g. acarbose and amylin), and other targets of action (e.g. pirenzepine and insulin-like growth factor-1 [IGF-1], which reduce growth hormone secretion, and glucagon-like peptide-1, which acts to stimulate insulin secretion). Many of these agents have been found to be effective in short-term studies with decreases in glycosylated hemoglobin of 0.5-1.0%, lowered postprandial blood glucose levels, and decreased daily insulin doses. Adverse effects such as poor gastrointestinal tolerability (metformin, acarbose) or potential acceleration of retinopathy (IGF-1) indicates the need for further studies of efficacy, safety, and patient selection before these adjunctive therapies can be widely recommended in type 1 diabetes.

Adolescent↗
PubMed2004

Metabolic control in adolescent girls: links to relationality and the female sense of self.

OBJECTIVE: This study investigated whether intimacy and autonomy in mother-daughter interactions and relational aspects of the self are associated with metabolic control in adolescent girls with type 1 diabetes. RESEARCH DESIGN AND METHODS: This cross-sectional study included 88 girls with diabetes (mean age 14.9 +/- 2.2 years, diabetes duration 7.1 +/- 3.9 years, and HbA1c 8.9 +/- 1.6%) from the Diabetes Clinic at the Hospital for Sick Children in Toronto and their mothers. Teens completed a self-report measure assessing self-concept in eight domain-specific areas. Mothers and daughters engaged in a 7-min, videotaped, problem-solving task involving a diabetes-related conflict issue. Interactions were rated using a macroanalytic rating system to assess intimacy and autonomy in parent-teen relationships. Metabolic control was measured using HbA1c. RESULTS: Self-concept in domains of perceived behavioral conduct (P=0.003), social acceptance (P=0.03), romantic appeal (P=0.03), and close friendships (P=0.04) independently predicted HbA1c levels, together accounting for 30% of the variance. Also, the experience of emotional closeness (i.e., intimacy) rather than separateness (i.e., autonomy) in mother-daughter relationships was associated with lower HbA1c (P=0.03). CONCLUSIONS: Relational aspects of the self and the experience of emotional closeness in relationships are associated with metabolic control in adolescent girls. Efforts to improve metabolic control in girls should include enhancing the self-concept and the experience of relatedness in familial, peer, and patient-caregiver relationships.

Adolescent↗
PubMed2004

Disturbed eating behavior and eating disorders in preteen and early teenage girls with type 1 diabetes: a case-controlled study.

OBJECTIVE: To compare the prevalence of eating disturbances in preteen and early teenage girls with type 1 diabetes to their nondiabetic peers. RESEARCH DESIGN AND METHODS: A cross-sectional, case-controlled study of 101 girls with type 1 diabetes, ages 9-14 years, and 303 age-matched, female nondiabetic control subjects was conducted. Participants completed a Children's Eating Disorder Examination interview. Socioeconomic status, BMI, and diabetes-related variables were assessed. Groups were compared using chi(2) analyses. RESULTS: Binge eating; the use of intense, excessive exercise for weight control; the combination of two disturbed eating-related behaviors; and subthreshold eating disorders were all more common in girls with type 1 diabetes. Metabolic control was not related to eating behavior in this study population. CONCLUSIONS: Eating disturbances, though mostly mild, were significantly more common in preteen and early teenage girls with type 1 diabetes. Screening and prevention programs for this high-risk group should begin in the preteen years.

Adolescent↗
PubMed2003

Cardiac failure after initiation of insulin treatment in diabetic patients with beta-thalassemia major.

Diabetes mellitus is a complication of beta-thalassemia major. Two patients are described who developed severe cardiac failure after initiation or intensification of insulin treatment. We hypothesize that insulin-induced fluid retention combined with reduced cardiac reserve was responsible for the cardiac failure. Careful initiation of insulin treatment in these patients is important.

Adolescent↗
PubMed2003

Congenital hypothyroidism: a review of current diagnostic and treatment practices in relation to neuropsychologic outcome.

Because thyroid hormone is essential for normal brain development, children born with congenital hypothyroidism who lack thyroid hormone during a circumscribed period of early development are at risk of brain damage and mental retardation. Since the advent of newborn screening programs in the 1980s, the diagnosis and treatment of this condition are now provided in the first 2-3 weeks of birth in most regions. While this is usually sufficient to prevent mental retardation, the children so identified attain mildly reduced IQs from expectation, and may still experience subtle and specific neurocognitive deficits. Their particular deficits are related to the brief period of thyroid hormone insufficiency they undergo, especially factors reflecting the severity of hypothyroidism at the time of diagnosis, the duration of hypothyroidism in infancy, and thyroid hormones at time of testing. In this article, we review the specific kinds of deficits demonstrated by children with congenital hypothyroidism who were diagnosed by screening and treated early, as well as the factors associated with their disease and its management that contribute to these deficits. The disease-related factors that will be reviewed will include the etiology of hypothyroidism and severity of disease at the time of diagnosis, while the treatment-related factors will include age at onset of therapy, starting and subsequent dose levels, compliance, and treatment-adequacy issues. Also examined will be the effects of hormone levels at the time of testing. In addition, the role of moderating variables such as social, genetic, and environmental influences, as well as the child's gender, will be discussed. Furthermore, several new issues including the quality of subsequent management, ultimate outcome, and pregnancy will be additionally reviewed. In conclusion, while outcome in congenital hypothyroidism is substantially improved by screening, affected children do still experience mild neuropsychologic deficits. To reduce the impact of persisting deficits, further research is needed to determine the optimal starting dose for the different etiologies, guidelines for subsequent management, and alternative therapies. Moreover, now that the original samples are reaching adulthood and, in females, childbearing age, further research is also needed regarding treatment during pregnancy in women with congenital hypothyroidism, as is research to determine how this population ultimately fares in adulthood.

Age Factors↗
PubMed2003

Metformin as an adjunct therapy in adolescents with type 1 diabetes and insulin resistance: a randomized controlled trial.

OBJECTIVE: To evaluate whether, in adolescents with type 1 diabetes, the addition of metformin to insulin and standard diabetes management results in 1) higher insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units per kilogram per day) and BMI. RESEARCH DESIGN AND METHODS: This was a randomized, placebo-controlled 3-month trial of metformin therapy in 27 adolescents with type 1 diabetes, high insulin dosage (>1 unit. kg(-1). day(-1)), and HbA1c >8%, with measurements of insulin sensitivity (by frequently sampled intravenous glucose tolerance test [FSIGT]), HbA1c, insulin dosage, and BMI at the onset and end of treatment. RESULTS: At t = 0, HbA1c was 9.2 +/- 0.9%, insulin dosage was 1.2 +/- 0.2 units. kg(-1). day(-1), fasting glucose was 10.6 +/- 2.4 mmol/l, and BMI was 24.2 +/- 3.9 kg/m2 (means +/- SD), with no difference between the metformin and placebo groups. At the end of the study, HbA1c was 0.6% lower in the metformin group than in the placebo group (P < 0.05). This was achieved at lower daily insulin dosages (metformin group -0.14 +/- 0.1 vs. placebo group 0.02 +/- 0.2 units. kg(-1). day(-1); P < 0.05), with no significant change in BMI. Fasting glucose levels improved significantly in the metformin group (P < 0.05). Change in insulin sensitivity, measured by FSIGT, was not significantly different between the two groups at study end. Mild hypoglycemia occurred more frequently in the metformin-treated than in the placebo subjects (1.75 +/- 0.8 vs. 0.9 +/- 0.4 events. patient(-1). week(-1); P = 0.03). There were no differences in frequency of severe hypoglycemic episodes or gastrointestinal complaints between the two groups. CONCLUSIONS: Metformin treatment lowered HbA1c and decreased insulin dosage with no weight gain in teens with type 1 diabetes in poor metabolic control. Changes in insulin sensitivity were not documented in this study using the FSIGT. Long-term studies will determine whether these improvements are sustained and whether certain subgroups accrue greater benefit from this therapy.

Adolescent↗
PubMed2003

Prolactin levels during long-term risperidone treatment in children and adolescents.

BACKGROUND: This analysis was designed to investigate prolactin levels in children and adolescents on long-term risperidone treatment and explore any relationship with side effects hypothetically attributable to prolactin (SHAP). METHOD: Data from 5 clinical trials (total N = 700) were pooled for this post hoc analysis. Children and adolescents aged 5 to 15 years with subaverage intelligence quotients and conduct or other disruptive behavior disorders received risperidone treatment (0.02-0.06 mg/kg/day) for up to 55 weeks. Outcome measures analyzed included serum prolactin levels, reported adverse events, and the conduct problem subscore of the Nisonger Child Behavior Rating Form. RESULTS: Mean prolactin levels rose from 7.8 ng/mL at baseline to a peak of 29.4 ng/mL at weeks 4 to 7 of active treatment, then progressively decreased to 16.1 ng/mL at weeks 40 to 48 (N = 358) and 13.0 ng/mL at weeks 52 to 55 (N = 42). There was no relationship between pro-lactin levels and age. Females returned to a mean value within the normal range (</= 30 ng/mL) by weeks 8 to 12, and males were close to normal values (</= 18 ng/mL) by weeks 16 to 24. At least 1 SHAP was reported by 13 (2.2%) of 592 children. There was no direct correlation between prolactin elevation and SHAP. CONCLUSION: With long-term risperidone treatment in children and adolescents, serum prolactin levels tended to rise and peak within the first 1 to 2 months and then steadily decline to values within or very close to the normal range by 3 to 5 months.

Adolescent↗
PubMed2002

Insulin injection regimens and metabolic control in an international survey of adolescents with type 1 diabetes over 3 years: results from the Hvidore study group.

UNLABELLED: The optimal insulin regimen for paediatric patients with type 1 diabetes remains controversial. Therefore this multicentre study was performed in adolescents over a 3-year period to assess metabolic control, severe hypoglycaemia, and weight gain in relation to insulin injection regimens. Out of 2873 children and adolescents in an international survey in 1995, 872 adolescents (433 boys, 439 girls, mean age in 1995 11.3+/-2.2 years) were restudied in 1998, relating insulin regimens to HbA(1c) measured in a central laboratory. In addition, the daily dose of insulin, changes in body mass index (BMI), and events of severe hypoglycaemia were evaluated. Over 3 years, the use of multiple injection regimens increased from 42% to 71%: 251 patients remained on twice daily insulin, 365 remained on multiple injections and 256 shifted from twice daily insulin to multiple injections. In all three subgroups an increase in insulin dose, a deterioration of metabolic control, and an increase in BMI were observed. Metabolic control deteriorated less than expected over 3 years during adolescence (HbA(1c) 1995: 8.7+/-1.6%; 1998 observed: 8.9+/-1.6%, HbA(1c) expected for 1998: 9.0%). BMI increased more than expected, the increase was greatest in patients switching from twice daily to multiple injections, and higher in females compared to males. CONCLUSION: in this international study, metabolic control was unsatisfactory in many adolescents with type 1 diabetes irrespective of the insulin regimen. No improvement in metabolic control was observed in this cross-sectional survey, over 3 years in any of the subgroups. Even the group switching from twice to multiple injections did not improve blood glucose control and the increase in body mass index was most pronounced in this group. Conclusive evidence, however, should be based on prospectively planned, randomised therapeutic trials in paediatric patients.

Child↗
PubMed2002

The effects of psychoeducation on disturbed eating attitudes and behavior in young women with type 1 diabetes mellitus.

OBJECTIVE: This study aimed to evaluate the effect of a six-session psychoeducation (PE) program on young women with type 1 diabetes mellitus (DM) and disordered eating attitudes and behavior. METHOD: Two hundred twelve young women attending a pediatric diabetes clinic were screened for signs of eating disturbance. Of these women, 130 passed the screening and were invited to participate in the intervention phase of the study. Eighty-five subjects were randomized to the PE or treatment-as-usual group. Assessments were conducted before and after treatment and at 6-month follow-up. RESULTS: Intention-to-treat group by time multivariate analyses of variance (MANOVAs) indicated significant reductions following PE treatment on the Restraint and Eating Concern subscales of the Eating Disorder Examination (EDE) and on the Drive for Thinness and Body Dissatisfaction subscales of the Eating Disorder Inventory (EDI), but no improvement in frequency of purging by insulin omission or hemoglobin A1c levels. DISCUSSION: The PE group was associated with reductions in eating disturbance, but not with improved metabolic control.

Adolescent↗
PubMed2002

Eating disorders in young women with type 1 diabetes mellitus.

Research findings from the past decade regarding the association of type 1 diabetes mellitus and eating disorders are critically reviewed in this paper. Although there has been much debate regarding the specificity of this association, a recent large multisite case-controlled study demonstrated that the prevalence rates of both full syndrome and subthreshold eating disorders among adolescent and young adult women with diabetes are twice as high as in their nondiabetic peers. Further, a 4-year follow-up study showed that disordered eating behavior in young women with diabetes often persists and is associated with a threefold increase in the risk of diabetic retinopathy. These eating disturbances tend to be associated with impaired family functioning and with poor diabetes management. Health care professionals should maintain a high index of suspicion for the presence of an eating disturbance among young women with diabetes, particularly among those with persistently poor metabolic control and/or weight and shape concerns. Screening for such disturbances should begin during the prepubertal period among girls with diabetes. A brief psychoeducational intervention leads to a reduction in disturbed eating attitudes and behavior but is not sufficient to improve metabolic control. More intensive treatment approaches, which should include a family-based component, may be needed to improve metabolic control. The evaluation of these and other treatment approaches is indicated in view of the serious short- and long-term health risks associated with eating disorders in young women with diabetes.

Adolescent↗
PubMed2002

Diabetic ketoacidosis and cerebral edema.

Cerebral edema is the leading cause of death in children presenting in diabetic ketoacidosis and occurs in 0.2 to 1% of cases. The osmolar gradient caused by the high blood glucose results in water shift from the intracelluar fluid (ICF) to the extracellular fluid (ECF) space and contraction of cell volume. Correction with insulin and intravenous fluids can result in a rapid reduction in effective osmolarity, reversal of the fluid shift and the development of cerebral edema. The goals for treatment should be a combination of intravenous fluid and insulin that results in a gradual reduction of the effective osmolarity over a 36- to 48-hour period, thereby avoiding rapid expansion of the ICF compartment and brain swelling.

Animals↗
PubMed2002

Islet cell transplantation and other new technologies for treating type 1 diabetes: a paediatric view.

Recent advances in diabetes care have facilitated the achievement and maintenance of excellent metabolic control. New insulin pumps and continuous glucose monitoring systems provide cause for optimism that an artificial pancreas may soon be developed. In addition, transplantation biology has advanced to the point where pancreas and islet transplants are being performed with increasing frequency. Recent reports suggest that improved techniques for isolation of islets and immune suppression may allow these procedures to become more commonplace. However, serious questions regarding long-term safety and efficacy need to be answered in older individuals before consideration is given to their more routine use in children and adolescents with diabetes.

Blood Glucose↗
PubMed2002

Deteriorating diabetes control during adolescence: physiological or psychosocial?

Metabolic control often worsens during the pubertal years in individuals with type diabetes mellitus (DM). This may be due in part to the developmental transition from dependency on parents to a more autonomous lifestyle. Adolescence is also marked by challenging of authority figures and previous ways of thinking, experimentation, and, in some female teenagers, emergence of disordered eating attitudes and behaviors. The insulin resistance of puberty may be particularly maladaptive for the teenager with type 1 DM and is likely under-recognized. In this review, we examine the impact of physiological and psychosocial changes during puberty in type 1 DM, highlight treatment strategies aimed at modifying these factors, and suggest further interventions that warrant evaluation.

Adolescent↗
PubMed2002

Recent trends in hospitalization for diabetic ketoacidosis in ontario children.

OBJECTIVE: To investigate trends and geographic variation in diabetic ketoacidosis (DKA) hospitalization rates among children in Ontario from 1991 to 1999. RESEARCH DESIGN AND METHODS: Canadian Institute for Health Information (CIHI) data were used to identify 15,872 diabetes-related hospital admissions in children younger than 19 years in Ontario from 1991 to 1999. Of these, 5,008 admissions were because of DKA and 10,864 admissions were because of conditions other than DKA (non-DKA). Small area variation analysis was used to compare areas with high versus low DKA admission rates. RESULTS: There was a 19% relative decrease in the overall diabetes admission rate over the study period. Non-DKA admissions decreased by 29%, whereas DKA admissions remained stable. Total days of care decreased by 393 days per year for non-DKA admissions and by 99 days per year for DKA admissions. The average length of hospital stay decreased from 4.9 to 3.5 days for non-DKA admissions and from 4.5 to 3.2 days for DKA admissions. The fatality rate was 0.19% for non-DKA admissions and 0.18% for DKA admissions. Variation across geographic areas remained stable for DKA over the study period (Kendall's correlation coefficient 0.64, P = 0.017) with an average 3.7-fold difference between the lowest and highest regions. CONCLUSIONS: Increased ambulatory care efforts for children with type 1 diabetes in Ontario have successfully reduced non-DKA admission rates. However, DKA admission rates have remained stable. Geographic variation for DKA admissions is low, but the observed 3.7-fold difference is clinically important for a preventable complication with a significant potential for long-term morbidity and mortality. Prevention strategies are needed, particularly in areas identified with the highest rates.

Adult↗
PubMed2002

[Eating disturbances in adolescent girls with type 1 diabetes mellitus].

Eating disorders that meet DSM-IV criteria, especially bulimia nervosa and EDNOS are more than twice as common in adolescent girls with Type 1 Diabetes (DM) than in their nondiabetic peers. The prevalence of subthreshold eating disorders is especially high in this group and may be found in 14% of girls with DM. Insulin omission is a common weight loss behavior in girls with DM and eating disorders. Insulin omission and binge eating inevitably contribute to the increased rate of hyperglycemia and increased risk of long-term diabetes related medical complications, including retinopathy and nephropathy. The weight gain and dietary restrictions associated with diabetes treatment and the ready availability of insulin omission to promote weight loss are most likely responsible for this increased prevalence of eating disorders. A high index of suspicion for eating disorders is recommended in the diabetes clinic setting to enable early identification of disordered eating attitudes and behavior before they progress to clinical eating disorders. Clinic-based psychoeducational programs may be effective for prevention or early intervention. Severe eating disorders require more intensive intervention, tailored to address the DM context.

Adolescent↗