Altered adrenal and thyroid function in children with insulin-dependent diabetes mellitus

In 129 children, aged 12.6 +/- 3.8 years, affected by type 1 diabetes mellitus, the levels of dehydroepiandrosterone sulfate (DHEAS), cortisol, T3, fT3, T4, fT4, rT3, TSH, cholesterol, and triglycerides were evaluated and compared with those of a control group of 458 healthy age-matched children. The results were also correlated with hemoglobin HbA1C. The DHEAS-standard deviation score (DHEAS-SDS; -0.36 +/- 0.77) was significantly different from zero in diabetic children, while the cortisol serum level was higher than in control subjects (485 +/- 94 vs 359 +/- 132 nmol/l). Moreover, the DHEAS-SDS and DHEAS-SDS/cortisol ratio correlated negatively with HbA1c. Diabetic patients also showed lower T3 values (2.22 +/- 0.4 vs 2.32 +/- 0.3 nmol/l) and a higher rT3/T3 ratio (0.17 +/- 0.09 vs 0.15 +/- 0.05) than controls. There was a negative correlation between T3 and HbA1C. Cholesterol (4.77 +/- 1.08 vs 4.51 +/- 0.76 mmol/l) and triglycerides (0.82 +/- 0.53 vs 0.63 +/- 0.37 g/L) levels were higher in diabetic children and positively correlated with HbA1c, but not with DHEAS-SDS. We can therefore conclude that diabetes, particularly if poorly controlled, tends to induce a dissociation of cortisol and DHEAS secretion and a low T3 syndrome, similar to that seen in other illnesses.     

Autonomic neuropathy in diabetic children

OBJECTIVE: Evaluate the presence of cardiovascular autonomic nerve dysfunction in children and adolescents with insulin-dependent diabetes mellitus. METHODOLOGY: We studied 110 patients (54 male, 56 female) and 100 healthy sex and age-matched children. Autonomic nerve function was assessed by standard cardiovascular reflex tests: (1) Fall in systolic blood pressure in response to standing. (2) Heart rate in response to standing. (3) Beat-to-beat rate variation during deep breathing. (4) Quotient of heart rate during and after Valsalva manoeuvre. (5) Change in blood pressure response to sustained handgrip. The coefficient of variation of heart rate was determined from 150 systoles using a microcomputer-based technique. The lower limits of normal were defined according to statistical analysis taking into account the relationship between heart rate variability and age. RESULTS: Forty-seven of the 110 diabetic children and adolescents studied showed one or more abnormal tests for cardiovascular autonomic dysfunction; many patients had an abnormality in more than one test. Twenty-two patients showed early involvement, 18 patients had definite and 7 severe involvement. No correlation was found between sex, glycaemic control, duration of diabetes or presence of retinopathy and persistent microalbuminuria and the autonomic nerve function. CONCLUSIONS: In the paediatric age group also, autonomic nerve dysfunction can be present in asymptomatic diabetic patients. Heart rate variation during Valsalva manoeuvre and maximum/minimum 30:15 ratio are the most sensitive indices to detect autonomic abnormalities in children.     

The association of non-insulin-dependent diabetes mellitus and cognitive function in an older cohort

This is the first demonstration of the use of accelerator mass spectrometry (AMS) as a tool for the measurement of 3H with attomole (10(-18) mol) sensitivity in a biological study. AMS is an analytical technique for quantifying rare isotopes with high sensitivity and precision and has been most commonly used to measure 14C in both the geosciences and more recently in biomedical research. AMS measurement of serially diluted samples containing a 3H-labeled tracer showed a strong correlation with liquid scintillation counting. The mean coefficient of variation of 3H AMS based upon the analysis of separately prepared aliquots of these samples was 12%. The sensitivity for 3H detection in tissue, protein, and DNA was approximately 2-4 amol/mg of sample. This high sensitivity is comparable to detection limits for 14C-labeled carcinogens using 14C AMS and demonstrates the feasibility of 3H AMS for biomedical studies. One application of this technique is in low-dose, dual-isotope studies in conjunction with 14C AMS. We measured the levels of 3H-labeled 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 14C-labeled 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in rat liver tissue and bound to liver DNA and protein 4.5 h following acute administration of individual or coadministered doses in the range of 4-5100 pmol/kg of body weight. Levels of PhIP and MeIQx in whole tissue and bound to liver protein were dose-dependent. MeIQx-protein and -DNA adduct levels were higher than PhIP adduct levels, which is consistent with their respective carcinogenicity in this organ. Coadministration of PhIP and MeIQx did not demonstrate any measurable synergistic effects compared to administration of these compounds individually. These studies demonstrate the application of AMS for the low-level detection of 3H in small biological samples and for its use in conjunction with 14C AMS for dual-labeling studies.     

Autonomic nervous function of the patients with neurally mediated syncope

Although diagnosis of neurally mediated syncope (NMS) using head-up tilt (HUT) test has been established, the exact mechanism of NMS has not yet been elucidated. We evaluated beta and alpha-adrenergic function in NMS patients by pharmacological autonomic function test. The alpha-adrenergic sensitivity of NMS patients was significantly lower than that of control subjects. The patients who need low dose isoproterenol for provocation of syncope showed higher beta-adrenergic sensitivity than patients who developed syncope without isoproterenol. Thus, pharmacological autonomic function test was useful for evaluation of NMS patients.     

Riboflavin deficiency in children with diabetes mellitus

Twenty-four insulin-dependent diabetic children and 114 normal control children, all between the ages of 6 to 16 years, were investigated for riboflavin deficiency. The method used was a measurement of erythrocyte glutathione reductase activity and the results were expressed as the activity coefficient (AC). None of the children had received vitamin supplementation. The percentage of diabetic children with riboflavin deficiency was 4 fold greater than in non diabetics. Supplementation with daily oral riboflavin quickly returned all AC values to normal.     

Autonomic nervous function in progressive supranuclear palsy--comparison with Parkinson's disease and healthy controls

This study evaluated the autonomic nervous function in 6 patients with progressive supranuclear palsy (PSP). The autonomic nervous functions in PSP patients were compared with those in 17 patients of Parkinson's disease (PD) and 9 age-matched healthy control subjects. Results were that all PSP patients and 59% of PD patients had sympathetic skin response (SSR) abnormalities. Significant abnormalities in cardiovascular response observed in PD patients suggested the presence of sympathetic and parasympathetic disturbances. There were no significant differences between PSP patients and control subjects in cardiovascular responses. But some of PSP patients showed abnormal cardiovascular responses compared with the results from the control subjects. In PSP patients mild disturbances in cardiovascular responses and sudomotor dysfunction were suggested. We consider that the high incidence of SSR abnormality is at least partially related to the presence of disturbances in the frontal lobes.     

Autonomic components of voluntary reaction in children with different ratios of direct and verbal stimuli

Interconnection between effector vegetative components of voluntary activity in children (6 to 7 years) has been studied on a model of arithmetic count with a different ratio of direct (kinesthetic, visual) and verbal stimuli. It has been shown that perception and processing of direct signals set up optimal conditions of vegetative providing for voluntary activity in children. A statistically significant correlation has been found between the characteristics of interconnection of vegetative components (relationship betwpen the heart rate and arterial pressure) and the level of capacity for mental work ("efficiency coefficient"). This dependence suggests that the neurodynamics in vegetative providing for voluntary reactions reflects the functional state of higher integrative brain activity in children.     

Thyroid function in a population of children with attention deficit hyperactivity disorder

4-Fluoro-3-nitrobenzoic acid attached to a solid support was shown to react under mild conditions with a wide range of functionalized phenols to yield, after cleavage, the corresponding biaryl ethers in excellent purity. In a similar fashion, biaryl thioethers could be obtained. Further elaboration of immobilized biaryl ethers demonstrates the potential for combinatorial library generation.     

Executive function in parents of children with autism

BACKGROUND: Previous studies have shown that individuals with autism show impaired performance on tests of executive function (Ozonoff et al. 1991, 1993; Hughes & Russell, 1993; Hughes et al. 1994). There is also strong evidence for genetic involvement in autism (see Rutter, 1991 for review). If executive dysfunction is a core impairment in autism, then similar impairments are hypothesized to exist in a subtler form among the parents of autistic children. METHODS: Forty parents of autistic children were compared with 40 parents of learning disabled children and 36 adults from unaffected families on three computerized tests of executive function. These tasks tapped attentional-shifting skills, visuospatial planning and working memory. Participants also received a computerized control test of spatial memory-span. In addition, the interviewer's initial impressions of family members were coded using a new 33-item questionnaire. RESULTS: A significant proportion of parents of autistic children (especially fathers) showed impaired executive function. By contrast, parents did as well as both comparison groups on a control test of spatial span, and on other 'non-executive' measures from the tasks, indicating that the autism group were as able and motivated as comparison groups. Interestingly, impairment of executive function was significantly correlated with the interviewer's pre-test impression of social abnormality among parents of autistic children. CONCLUSIONS: The hypothesis that a significant proportion of parents of autistic children show impaired executive function was supported. Parents showed good memory ability, but relatively poor planning skills and attentional flexibility. The extent to which this is an inherent trait in family members, rather than a reflection of the difficulties involved in caring for an autistic child, remains to be examined.     

New developments in treating children with insulin-dependent diabetes mellitus

A number of new developments in the management of insulin-dependent diabetes mellitus have occurred in the past several years. Primary care providers including pediatric nurse practitioners need to be aware of these developments so that they can work effectively with specialty providers in caring for children with insulin-dependent diabetes mellitus. This article discusses the implications of the Diabetes Control and Complications Trial for children and adolescents, the Diabetes Prevention Trial-Type I, and several other recent developments in caring for children with insulin-dependent diabetes mellitus.     

Growth changes in children and adolescents with short-term diabetes

OBJECTIVE: Height and weight changes during the first 3 years of diabetes were prospectively followed in 152 diabetic children and adolescents. RESEARCH DESIGN AND METHODS: The study sample consisted of 152 Caucasian diabetic patients (84 boys; 68 girls) followed from diabetes onset in the Paediatric Diabetes Unit and 80 Caucasian normal subjects (49 boys; 31 girls) assessed in the Outpatient General Paediatric Clinic of the same hospital for routine examination and not affected by problems that might influence growth. Diabetic patients and control subjects were consecutively enrolled in the study between 1989 and 1992; diabetic patients with positive markers for celiac disease (positive antiendomysial antibodies) and thyroid disease (positive antimicrosomial antibodies) or any other chronic disease were not considered in the study. Mean age of diabetic patients (8.9 +/- 4.1 years) and control subjects (8.5 +/- 4.2 years) at recruitment in the study was similar. RESULTS: At onset of diabetes, the mean height expressed as the height standard deviation score (HSDS) was significantly greater than the expected values (P < 0.0001) and was independent of sex and pubertal stage. During the first 3 years of diabetes, HSDS decreased significantly (F = 6.9; P < 0.001). Meanwhile, growth velocity as standard deviation score (SDS) decreased significantly between the 1st and 2nd year (-0.12 +/- 2.1; -0.76 +/- 2.6, respectively; P < 0.05), but it was similar between the 2nd and 3rd year of diabetes. Weight expressed as SDS increased significantly during the first 2 years of diabetes but not thereafter. Height changes during the study period were independent from pubertal stage and sex. Metabolic control and insulin requirement, in our series, were not clearly related to height and weight changes. CONCLUSIONS: Diabetic patients at onset of diabetes are taller than age- and sex-matched nondiabetic subjects. During the first years of the disease, linear growth decreases independently of metabolic control and weight changes.     

Relative nocturnal hypertension in children with insulin-dependent diabetes mellitus

Twenty-four-hour blood pressure and heart rate measurements were carried out in 14 newly diagnosed diabetics and in 28 diabetics with 5-13 years' duration of the disease; 8 healthy children were used as controls. Mean arterial blood pressure increased at night in 5, decreased slightly (less than 10%) in 5 and decreased markedly (more than 10%) in 18 diabetics with longer duration of the disease. The diurnal-nocturnal differences in heart rates were significantly lower in diabetics with relative "nocturnal hypertension" compared to the control group (p < 0.05). A significant negative correlation was found between maximal arterial blood pressure during physical exercise and the diurnal-nocturnal differences in mean arterial blood pressure in diabetics (r = -0.58; p < 0.02). In conclusion, we found elevated nocturnal blood pressure in a subgroup of children with longer duration of diabetes and without increased albumin excretion. However, longitudinal studies of blood pressure profiles are needed to identify the candidates for diabetic vasculopathy among diabetic children.     

Autonomic control of cardiovascular function: clinical evaluation in health and disease

The high- and low-pressure baroreceptor reflexes are integral to the control of blood pressure by the autonomic nervous system. Tests of the integrity of these baroreflexes make it possible to identify the site of autonomic dysfunction in patients with orthostatic hypotension. Clinical characteristics and typical results of autonomic testing in patients with autonomic failure, with carotid sinus hypersensitivity, and with hyperadrenergic autonomic dysfunction are described in this review.     

Consistency of pupillary abnormality in children and adolescents with diabetes

Repeat measurements on pupillary adaptation to darkness were performed in a cohort of 66 children and adolescents with insulin-dependent diabetes mellitus (IDDM) (initial age 6.9-17.0 years) after a mean interval of 3.5 years, using a portable pupillometer. While there was a close correlation between the results of the two studies (r = 0.94, p < 0.001), the pupillary dilatation, the ratio of the pupil diameter to the iris diameter % (PD%), had decreased significantly (61.5% vs 62.9%, p < 0.001) over these 3.5 years in children with diabetes. The same measurements were performed on 89 healthy control children in the first study and 66 in the reassessment period and PD% was not significantly different in the two control groups. Five children with diabetes identified as having abnormal pupillary dilatation in the first study were outside the normal range 3.5 years later. In addition 4 children in whom initial testing had been normal, showed abnormality at the time of the second study. None of these children had symptoms of autonomic neuropathy. These findings suggest that abnormality in pupillary adaptation in diabetic children is consistent and increases with time and may serve as an early marker of tissue damage associated with diabetes.     

Physical activity and glycaemic control in children with diabetes mellitus

We report nine case histories of patients admitted to a psychiatric hospital for severe somatic disorders. The somatic disease was either the cause of the psychiatric symptomatology, or it occurred in addition to a well-known psychiatric disorder. For general practitioners and psychiatrists it can be difficult to differentiate between symptoms due to psychiatric disorders and symptoms that indicate somatic disorders. If patients refuse the necessary diagnostic or therapeutic procedures and show behaviour that is not related to good health, there is increased risk for complications and increased morbidity.     

Growth and sexual maturation in children with insulin-dependent diabetes mellitus

Prediabetes, the interval preceding the clinical recognition of diabetes mellitus, is believed to consist of several months or years of beta-cell destruction associated with no clinically recognized signs other than possible increased growth velocity. This increased growth rate may be the result of increased insulin, increased growth hormone, or both. As insulin-dependent diabetes approaches clinical recognition, insulin deficiency becomes manifest as slowing of growth velocity and more obvious weight loss. If a prepubertal child has insulin-dependent diabetes mellitus, sexual maturation is frequently delayed and physical growth is adversely affected. Insulin is an anabolic hormone that regulates metabolic pathways involved in the production of protein, glycogen, and fat. The normal release of growth hormone and the hepatic production of insulin-like growth factor I is modulated by the action of insulin. The absence of physiologic insulin response leads to dysfunctional quantities of growth hormone, insulin-like growth factor I, and sex hormones, resulting in growth impairment and delayed sexual maturation. Delayed sexual maturation may cause concern because it has a major impact on growth and maturation of children. However, there is evidence that sex hormones have a stimulating effect on the tissue damage associated with chronic hyperglycemia. The loss of physiologic insulin release significantly affects physical growth, sexual maturation, and the chronic complications associated with insulin-dependent diabetes mellitus.