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Biomedical subjects

W L Clarke

Publications and source records attributed to W L Clarke.

At least 37 records · Page 2Linked to original sources

Individual differences in neurobehavioral disruption during mild and moderate hypoglycemia in adults with IDDM.

This study investigated the neurobehavioral effects of mild and moderate hypoglycemia in adults with insulin-dependent diabetes mellitus (IDDM). On 2 consecutive days, 26 subjects were tested in a counterbalanced, randomized, single-blind, crossover design. On the experimental day, subjects performed tests at 6.4, 3.6, and 2.6 mmol/l and again after glycemic recovery to 6.3 mmol/l. On the control day, subjects performed tests four times at euglycemia. Three months after testing, 15 subjects repeated the experimental day protocol. Results demonstrated that both mild and moderate hypoglycemia significantly disrupted performance. However, performance deterioration varied substantially across individual subjects. Men exhibited significantly more deterioration than women at mild hypoglycemia, and subjects with a history of unconsciousness due to hypoglycemia exhibited more deterioration than subjects with no such history. Individual deterioration scores during repeat testing significantly correlated with performance during original testing. Recovery from hypoglycemia-related impairment varied across individuals and was correlated with degree of impairment during hypoglycemia. These results suggest that the glycemic threshold for onset and recovery from neurobehavioral deterioration with hypoglycemia, as well as degree of impairment experienced, varies across individuals. Furthermore, these individual differences are stable across time.

Adult↗

Alterations in growth hormone secretion and clearance in adolescent boys with insulin-dependent diabetes mellitus.

At puberty, elevated circulating GH concentrations are found, with a parallel increase in the levels of insulin-like growth factor-I (IGF-I). However, these hormonal changes are less well understood in children with insulin-dependent diabetes mellitus (IDDM) during the peripubertal years. Since the metabolic derangement is often associated with elevated circulating GH and diminished serum IGF-I levels, we sought to determine whether similar alterations occur in boys with IDDM. A multiple parameter deconvolution analysis was applied to serum GH concentrations measured at 20-min intervals for 24 h in 25 boys with IDDM. Subjects were divided into 3 pubertal groups, pre (n = 9), early (n = 8), and late (n = 11), according to Tanner stage. Glycosylated hemoglobin and body mass index-SD scores were indistinguishable among groups. Forty nondiabetic peripubertal boys served as controls. Similar to those in the normal boys, circulating GH concentrations and serum IGF-I levels increased during puberty in the boys with IDDM. The augmented circulating GH concentrations occur due to an increase in GH secretion, as determined by calculated daily GH production rates (760 +/- 119 vs. 1025 +/- 121 vs. 1821 +/- 266 micrograms/day, respectively for the 3 groups). IGF-I levels were decreased in prepuberty in the boys with IDDM and were overcome with increasing pubertal development (0.68 +/- 0.13 vs. 0.78 +/- 0.11 vs. 1.53 +/- 0.20 U/mL; P < 0.05). There was an increase in the maximal rate of GH secretion per burst (amplitude) during prepuberty (0.54 +/- 0.05 vs. 0.88 +/- 0.17 microgram/L.min, control vs. IDDM; P = 0.03) and early puberty (0.64 +/- 0.10 vs. 0.88 +/- 0.10 microgram/L.min; p = 0.04). The differences in amplitude between the controls and the boys with IDDM were absent once puberty was well established (1.00 +/- 0.10 vs. 1.02 +/- 0.14 microgram/L.min; P > 0.05). The metabolic clearance of GH was increased in the late pubertal boys with IDDM compared to that in their controls (GH half-life, 24.0 +/- 1.0 in control vs. 19.8 +/- 0.5 min in diabetics; P = 0.006). We conclude that comparable increments in GH secretion and serum IGF-I levels in boys with IDDM in moderate glycemic control and controls are presumably related to increased levels of testosterone in both groups. However, differences exist with respect to GH secretory burst amplitude (augmented) and serum IGF-I concentrations (decreased) before puberty is reached. These alterations disappear with the establishment of puberty.

Adolescent↗

Disruptive effects of acute hypoglycemia on speed of cognitive and motor performance.

OBJECTIVE: To directly examine whether hypoglycemia differentially slows cognitive versus motor function, to evaluate the reliability of hypoglycemic-related slowing, and to examine factors contributing to individual differences. RESEARCH DESIGN AND METHODS: IDDM subjects (n = 10) were administered a pure cognitive and a pure motor neuropsychological test at euglycemia (5.4 mmol), blood glucose nadir (2.6 mmol), postnadir (3.6 mmol), and again at euglycemia (6.7 mmol). To assess the practice effect, matched control subjects were tested at similar time intervals. RESULTS: Concurrent and test-retest reliability for all tests was robust (r = 0.68-0.94). Only cognitive tasks demonstrated impairment at nadir (P < 0.04). Individual differences, in terms of cognitive impairment, were significantly correlated with levels of blood glucose at nadir and baseline performance. CONCLUSIONS: Cognitive tasks appear to be more sensitive to neuroglycopenia than motor tasks. Cognitive impairment caused by hypoglycemia is reliable and differs across subjects. Individuals who show reliable sensitivity to cognitive impairments of hypoglycemia should avoid moderately low blood glucose levels.

Adult↗

Perceived symptoms in the recognition of hypoglycemia.

For people with diabetes, detection of hypoglycemic symptoms is a critical tool for the recognition and treatment of hypoglycemia. This is not a simple process involving only the occurrence of a hypoglycemic-relevant physiological event, such as sweating. We propose a four-step biological and psychological model that leads to the accurate recognition of hypoglycemia through symptoms. The model illustrates both the chronic and transient modifiers that can enhance and interfere with recognition of hypoglycemia. Three common methods are used to investigate the occurrence and utility of hypoglycemic symptoms that relate to this model. This article reviews the advantages and disadvantages of these methods, providing previously unpublished illustrative data. The field study hit/false alarm approach was shown to be the most useful method. The relevance of this model and data to the concept of hypoglycemic awareness/unawareness and blood glucose awareness training is discussed.

Adult↗

Parental and professional estimates of self-care independence of children and adolescents with IDDM.

OBJECTIVE: To report the results of a survey of 490 parents of children with insulin-dependent diabetes mellitus (IDDM) regarding the children's mastery of 38 diabetes-care skills. Parental responses are contrasted with those of a previous survey in which 229 diabetes professionals estimated ages at which typical children with IDDM master the same skills. RESEARCH DESIGN AND METHODS: Parents were recruited at five pediatric endocrinology clinics with a response rate of 88.9%. RESULTS: For 33 of 38 skills, professionals' median mastery age estimates exceeded, by greater than or equal to 1 yr, the median ages that parents reported skill mastery by their estimates, children. Despite the parent-professional disagreement about mastery-age their survey responses yielded substantial agreement about the order of mastery of specific skills. The data also revealed two profiles of comparative results. For many items, parents reported earlier skill mastery, but parental and professional estimates eventually converged during adolescence. These skills consisted of rote, motoric acts, or more complex tasks for which errors yield relatively certain aversive consequences. For other skills, more professional estimated skill mastery among adolescents than did parents. These skills required substantial organization and self-regulation by the adolescent, involved treatment components for which the aversive consequences of errors are deferred and uncertain, or they were skills infrequently required of most patients with IDDM. CONCLUSIONS: The parent-professional discordance revealed by this survey illustrates the importance of clear specification of treatment responsibilities, careful monitoring of self-care competence, and periodic reeducation of children with IDDM.

Adolescent↗

Multifactorial origin of hypoglycemic symptom unawareness in IDDM. Association with defective glucose counterregulation and better glycemic control.

To assess potential relationships between unawareness of hypoglycemic symptoms and both defective glucose counterregulation and therapy-associated altered glycemic thresholds, symptoms and hormonal responses to hypoglycemia were quantitated during standardized insulin infusion tests in 41 patients with insulin-dependent diabetes mellitus (IDDM). The glycemic thresholds for both neurogenic and neuroglycopenic symptoms (and those for both epinephrine and pancreatic polypeptide release) were at lower plasma glucose concentrations in both patients with defective (n = 9, 22%) and those with adequate glucose counterregulation and, among the latter, in patients with lower compared with higher glycosylated hemoglobin levels. The data are consistent with the concept that both defective glucose counterregulation and improved glycemic control contribute to excessive hypoglycemia in IDDM by reducing awareness of symptoms of developing hypoglycemia and by impairing physiological defenses against hypoglycemia. Thus, hypoglycemic symptom unawareness is multifactorial in origin and may be partly reversible.

Awareness↗

Accuracy of blood glucose estimation by children with IDDM and their parents.

OBJECTIVE: To evaluate the accuracy of blood glucose symptom recognition and subjective blood glucose estimation in insulin-dependent diabetic (IDDM) children and their parents. RESEARCH DESIGN AND METHODS: Blood glucose estimation questionnaires were completed 4 times/day at home during routine activities. A sequential sample of 19 families, who attended a pediatric diabetes clinic, with IDDM children less than 12 yr old and IDDM duration of greater than or equal to 9 mo comprised the study. RESULTS: Error grid analysis showed that both children and parents demonstrated poor accuracy, making clinically significant errors as frequently as clinically accurate estimates. The most common error was the failure to detect extreme blood glucose levels, with a significant tendency to underestimate hyperglycemia. Children often reported hypoglycemia when blood glucose was hyperglycemic. Confidence in the ability to estimate blood glucose was unrelated to measured accuracy. CONCLUSIONS: IDDM children and their parents demonstrated a higher rate of blood glucose estimation errors than IDDM adolescents and adults in previous studies. Even in families who use self-monitoring of blood glucose frequently, self-reported ability to recognize symptoms and estimate blood glucose should be viewed with caution. Families with IDDM children need more education about errors in symptom recognition and blood glucose estimation. They should also be encouraged to use self-monitoring of blood glucose before treating children's reported hypoglycemic symptoms whenever possible.

Adult↗

Environmental stress and blood glucose change in insulin-dependent diabetes mellitus.

Blood glucose (BG) response to psychological stress in insulin-dependent diabetes mellitus (IDDM) patients has not been firmly established. We report a study designed to address the gaps and methodological difficulties reviewed. Subjects with IDDM were exposed to two sessions (12 weeks apart) of two 20-min standardized stressors (active and passive) and a control condition administered in counterbalanced order. To measure BG response, subjects were connected to a glucose/insulin infusion system providing continuous BG measurement. Mood checklist measures were obtained at prestressor, poststressor, and recovery periods. During the first session of testing, the active stressor was associated with significantly more absolute change in BG response than the passive stressor. Results also indicate that IDDM subjects' BG response to this active stressor was idiosyncratic but significantly reliable over time.

Arousal↗

Survey of diabetes professionals regarding developmental changes in diabetes self-care.

There are no empirically obtained data defining appropriate developmental expectations for the acquisition of self-care independence by children with insulin-dependent diabetes mellitus. This study surveyed diabetes professionals about their estimates of ages at which children typically master 38 diabetes skills. The 229 survey respondents represented a broad range of professions and clinical settings and had extensive experience as diabetes professionals. Mean mastery age estimates were less than 14 yr for the 38 skills assessed. Responses to each item were variable among respondents, with a mean SD of 2.1 yr in estimated mastery ages for all items. Estimated mastery ages were below the age ranges recommended by the American Diabetes Association for 14 of 20 comparable skills. Physicians generally expected the diabetes skills to be mastered at later ages than did nurses or other health-care professionals. There were no other consistent response patterns related to respondent characteristics, i.e., years of clinical experience, employment setting, current patient load, or method of survey distribution.

Adolescent↗

Treatment of the young child with postoperative central diabetes insipidus.

A continuous intravenous infusion of aqueous vasopressin (dosage range, 1.0 to 3.0 mU/kg/h) was administered to two patients (respective ages, 2 weeks and 3 years 1 month) who had postoperative central diabetes insipidus to determine if this mode of therapy is helpful in the very young patient. In both patients the polyuria and serum hyperosmolality were corrected. These findings suggest that an intravenous infusion of aqueous vasopressin can provide satisfactory control of the polyuria and electrolyte disturbances found in young children with acute postoperative central diabetes insipidus.

Brain↗

Stress in parents of children with diabetes mellitus.

The level of stress experienced in the parenting role by mothers of 49 children with insulin-dependent diabetes mellitus (IDDM) and its relationship to glycemic control was examined with the parenting stress index (PSI). A subsample of the research group of 25 children with diabetes (less than or equal to 11 yr old) was compared with an age-matched control group (n = 21) drawn from the original study of the PSI on total stress, parent- and child-domain, and subdomain scale scores. The two groups differed on one child-domain subscale, whereby children with diabetes are perceived by their mothers as more demanding than healthy controls. Three parent-subscale differences existed between the two groups, with mothers of children with diabetes reporting less attachment to their children, less spousal support, and poorer health. Analysis of the diabetes sample demonstrated significant stress on several of the child- and parent-domain subscales in a large proportion of the sample. Stress, at levels greater than or equal to 70th percentile of the control group, existed on the child scales of acceptability, mood, demanding behavior, and reinforcement for 51% of children with diabetes. Elevations associated with stress in the parenting role were evident on the scales associated with parental attachment, depression, and competence for 33% of parents. No differences in the level of glycosylated hemoglobin (HbA1) existed between children whose mothers reported high levels of stress in themselves and their children and those whose mothers reported little stress. Hierarchal regression analysis demonstrated a significant relationship between the child stress scale of distractibility, the use of self-monitoring blood glucose assessment, and low levels of HbA1.

Adult↗