Alterations of carbohydrate and lipoprotein metabolism in childhood obesity--impact of insulin resistance and acanthosis nigricans.

AIM: To study the prevalence of alterations of glucose and lipoprotein metabolism and the impact of acanthosis nigricans (AN) in childhood obesity. PATIENTS AND METHODS: 113 obese children, 57 with simple obesity (SO) and 58 with obesity and AN (OAN). Oral glucose tolerance test was performed, serum glucose, insulin and lipoprotein parameters were determined, and insulin resistance/sensitivity indices were calculated. RESULTS: Insulin resistance, basal and reactive hyperinsulinemia, impaired glucose tolerance (IGT) and dyslipidemia were found to be frequent conditions in children with OS as well as OAN. Reactive insulinemia was more pronounced in OAN than in SO, and insulin resistance was more frequent when AN was more prominent. Triglycerides were higher and HDL-C was lower, and atherogenic dyslipidemia was more frequent in OAN compared to SO. CONCLUSION: Children with obesity form a risk population. AN is a factor which can be used in metabolic risk factor clustering estimation in childhood obesity.

Alterations of glucoregulation in childhood obesity--association with insulin resistance and hyperinsulinemia.

AIM: To study the prevalence of alterations of glucoregulation in childhood obesity. PARTICIPANTS: 250 obese children. Oral glucose tolerance test was performed, serum glucose and insulin were determined, and HOMA-IR was calculated. RESULTS: Impaired fasting glucose (IFG) was found in 1.2% according to World Health Organisation criteria and 4.4% according to the criteria of the International Diabetes Federation. Impaired glucose tolerance (IGT) was found in 13.6%, type 2 diabetes mellitus (DM2) in 2.4%. Frequency of fasting glucose (FG) above 7.0 mmol/l was 1.2%. Basal hyperinsulinemia was increased in 70%, reactive hyperinsulinemia in 88%, frequency of elevated HOMA-IR was 78%. 120' insulin was increased in all cases with abnormal FG, IGT and DM2, HOMA-IR was elevated in 79% of patients with IGT and all patients with abnormal FG and DM2. Significant positive correlations were demonstrated between body mass index and insulin levels. CONCLUSION: Our data show that hyperinsulinemia can successfully compensate for insulin resistance in the majority of the obese children. Since IFG is less frequent than IGT there is a need for performing OGTT to demonstrate abnormality of glucoregulation in obese children.

Appropriate sampling times for growth hormone (GH) measurement during insulin tolerance testing (ITT) in children.

BACKGROUND: The Pfizer International Metabolic Database (KIMS), a large pharmacoepidemiologic database for adults with growth hormone deficiency (GHD), was recently analyzed to determine which tests are in use to assess GHD and how well they correlate. At the time of this analysis, a total of 15,724 tests had been reported to KIMS. The most frequently used is the insulin tolerance test (ITT), followed in order by the arginine stimulation test (AST), the glucagon stimulation test (GST) and the GH-releasing hormone+arginine (GHRH+arg) test. The ITT correlated with both the AST and the GST, but not with the GHRH+arg. CONCLUSIONS: For the AST and GST, use of a diagnostic threshold of 3 mug/l does not attenuate the effects of severe GHD.

Assessment of cardiovascular risk factors and their correlation in 28,000 Hungarians.

OBJECTIVES: The aim of this study was to assess the prevalence and inter-relations of systolic hypertension, hypercholesterolaemia and hyperglycaemia in more than 28,000 Hungarians. STUDY DESIGN AND METHODS: A retrospective study was designed to collect relevant information from the database of the Screening Institution in Miskolc, Hungary, between 1990 and 1998. Prevalence of the investigated conditions was compared between different groups. RESULTS: The occurrence of any of the investigated cardiovascular risk factors increased the likelihood of the other risk factors, and this relationship was most apparent in more serious categories. A particularly high degree of comorbidity was found between hypertension and hyperglycaemia. CONCLUSION: Since these results were based on a large percentage of the population, this study provides an important message for practising doctors: if they find any of these three risk factors in a patient, it is highly recommended that they should search for the others.

[Value of the waist-hip ratio in adolescent obesity]. / A derék- és csípökörfogat hányadosának értéke serdülök elhízásában.

Interrelationship between the body mass index (BMI), the waist-hip ratio (WHR) and serum concentration of immunoreactive insulin (IRI), C-peptide and sex hormone binding globulin (SHBG) was investigated in adolescents with obesity. Significant positive correlations were found between BMI and IRI, between BMI and C-peptide and there was a negative correlation between BMI and SHBG. WHR did not correlate with IRI, C-peptide and SHBG. IRI, C-peptide and SHBG in the group of central and gluteal obesity differentiated by WHR did not differ significantly. These results suggest that use of WHR to differentiate central and gluteal obesity does not help in adolescent period, possibly because of somatic changes of puberty.

[Relationship between immunoreactive insulin and plasma somatomedin-C/insulin-like growth factor-I concentration in childhood obesity]. / Osszefüggés a szérum immunreaktív insulin (IRI) és a plazma somatomedin-C/insulin-like growth factor-I (SM-C/IGF-I) koncentrációk között gyermekkori elhízásban.

Childhood obesity may be characterised by basal and reactive hyperinsulinemia, reduced growth hormone (HGH) responses to various provocative stimuli and increased plasma concentration of somatomedine-C/insulin-like growth factor-I (SM-C/IGF-I). For this reason the relationship between the degree of obesity (i. e. BMI), serum immunoreactive insulin (IRI) and plasma SM-C/IGF-I was investigated in children with obesity (n = 26, age: 13.0 +/- 0.97 years, BMI: 32.8 +/- 5.3 kg/m2). SM-C/IGF-I was increased in obese children compared to the normal range of this age. Significant positive correlations were found between BMI and IRI, between BMI and SM-C/IGF-I, and between IRI and SM-C/IGF-I. These results suggest that SM-C/IGF-I production in obesity is regulated by IRI dependent on BMI and this regulating effect of insulin may be important in obesity since HGH production to provocative stimuli is reduced.

[Insulin resistance in childhood obesity]. / Inzulin-rezisztencia a gyermekkori elhízásban.

Insulin binding to erythrocytes (IB) and serum immunoreactive insulin concentration (IRI) were measured and relationships between these parameters and body mass index (BMI) were investigated in obese children and age matched controls with normal body weight. IRI was increased and IB was decreased significantly in the obese group compared to data of the controls. The decreased IB was due to a decrease in insulin receptor number since it was not accompanied by alteration of half maximal inhibition dose (ID50). Strong negative correlations were found between BMI and IB and between IRI and IB while a positive association was seen between BMI and IRI. These results prove an interrelationship between weight excess, hyperinsulinism and insulin resistance in childhood obesity.

Insulin resistance in obese boys with acanthosis nigricans.

Insulin resistance was investigated in three obese boys with acanthosis nigricans and their results were compared to those obtained in non-acanthotic obese patients. Blood glucose immune reactive serum insulin and C-peptide during oral glucose tolerance test and 125I-insulin binding investigated. Obese patients with acanthosis nigricans were more insulin resistant than simple obese controls. Insulin binding studies performed in two acanthotic patients suggested that one of them had insulin resistance type A, and the second patient had insulin resistance type B. According to the results acanthosis nigricans can serve as a marker for severe insulin resistance in obesity.

Sex hormone binding globulin (SHBG) in children with obesity.

Serum sex hormone binding globulin (SHBG) concentration of children with obesity was measured and relationships between SHBG level and body mass index (BMI), waist hip ration (WHR), serum insulin, C-peptide, thyroid hormones (thyroxine--T4, triiodothyronine--T3/ sexual hormones (testosterone--T, oestradiol--E2) were investigated. Significant negative correlations were found between SHBG concentration and BMI, serum insulin, C-peptide concentration; significant positive concentrations were found between BMI and serum insulin, C-peptide concentration. Thyroid hormone and sexual hormones did not associate with SHBG levels. These results suggest that insulin hypersecretion has an important role in determining the reduction of SHBG production in obesity.

Brown adipose tissue cell respiration in hypo- and hyperthyroidism after stimulation with selective and non selective beta-adrenergic agonists.

Brown adipocyte respiration was measured in isolated cells from hypothyroid, hyperthyroid and euthyroid Sprague-Dawley male rats. Hypothyroidism was induced by providing drinking water containing methimazole and hyperthyroidism was induced by addition of thyroid powder to the diet. Brown adipose tissue (BAT) cells were isolated by collagenase digestion and oxygen consumption (VO2) was measured by Clark type oxygen electrodes. BAT cell respiration was stimulated by selective and nonselective beta-adrenergic agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Basal BAT cells respiration did not differ according to thyroid status. Maximal VO2 responses of BAT adipocytes from hypothyroid rats were significantly lower than in euthyroidism after ISO and BRL. The reduced response was more marked for ISO than for BRL. The thermogenic sensitivity was significantly greater in euthyroid than is hypothyroid cells for ISO, but not for BRL. The euthyroid-hyperthyroid differences were not significantly different. These results suggest: basal respiration of BAT cells in hypo- and hyperthyroidism does not reflect the overall changes in whole body metabolism; the decreased thermogenic response in hypothyroidism might be due to decreased beta-adrenoceptor numbers and/or decreased intracellular thyroxine-triiodothyronine conversion; changes in sensitivity to ISO and BRL in vitro reflect the changes seen in VO2 in vivo.

Thermogenic responses to selective and nonselective beta-adrenerg agonists in hypothyroidism of Sprague-Dawley rats.

Resting oxygen consumption (VO2) and mitochondrial GDP binding were measured in hypothyroid and euthyroid rats after administration of selective and nonselective beta-adrenoceptor agonists (BRL 35135A and Isoprenaline--BRL, ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-agonists were lower in hypothyroid rats than in the euthyroid group. The reduced response was more marked for ISO than for BRL. These results suggest that BRL is acting on a beta-adrenoceptor which differs from beta-1 and beta-2 adrenoceptors, responsible for the effect of ISO. Activation of thermogenesis via this beta-3 adrenoceptor seems to be less dependent on permissive levels of thyroid hormones than on activation via beta-1 and/or beta-2 adrenoceptors.

Late results of thyroid surgery for hyperthyroidism performed in childhood.

The authors report on the complex follow-up of 60 patients operated on for hyperthyroidism in childhood, on average 13.7 years after surgery. In 16.7% of the patients manifest hypothyroidism, in 45% subclinical hypothyroidism was found; 30% of the patients were euthyroid, and manifest hyperthyroidism recurred in 8.3%. Autonomous adenomas were enucleated in two children and three young adults. Severe disorders in thyroid function developed especially after the surgery of diffuse toxic goiters accompanied by ophthalmopathy. The disorders of humoral and cellular immunity were detected most frequently in recurrent manifest hyperthyroidism. There was no case where ophthalmopathy progressed after the operation. In the offspring of the operated patients the incidence of hyperthyroidism was not increased in childhood. The authors call attention to the importance of postoperative follow-up and hormone treatment.

Late prognosis of childhood and juvenile thyroid carcinomas.

The authors report on the biological properties and late prognosis of 16 children and juvenile patients operated on during the past 24 years for thyroid tumour who underwent regular followup. The clinical and morphological characteristics of the carcinomas are described, together with the late immune response of the patients undergoing complex treatment. The study is also concerned with the characteristics of the DNA content of the tumorous cell nuclei, the pregnancy success rate of the operated patients and the thyroid function of the children born.

Effects of hypothyroidism and hyperthyroidism on thermogenic responses to selective and nonselective beta-adrenergic agonists in rats.

Oxygen consumption (VO2) and mitochondrial guanosine diphosphate (GDP) binding of interscapular brown adipose tissue (BAT) were measured in hypothyroid, hyperthyroid and euthyroid rats after stimulations with selective and nonselective beta-adrenoceptor agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-adrenergic stimulations were lower in hypothyroid rats than in the euthyroid group. The reduced responses were more marked for ISO than for BRL. Restion VO2 and VO2 increment after beta-adrenergic stimulations were higher in hyperthyroid rats than in the eurthyroid group; the increment was more marked for BRL than for ISO. In hyperthyroidism, mitochondrial GDP binding after BRL and after ISO was in the same magnitude; it was higher in the hyperthyroid than in the euthyroid group after BRL but not after ISO. The different thermogenic responses after ISO and BRL stimulations suggest that BRL is acting on a beta-adrenoceptor differing from the beta-1 and beta-2 adrenoceptors responsible for the effects of ISO. Activation of thermogenesis via the beta-3 adrenoceptor seems to be less dependent on the permissive levels of thyroid hormones than activation via beta-1 and/or beta-2 adrenoceptors. The beta-3 adrenoceptor may be more sensitive to increased levels of thyroid hormones.

[Congenital hypophosphatasia as a possible cause of early loss of deciduous teeth]. / Congenitalis hypophosphatasia, mint a korai tejfog-vesztés lehetséges kóroka.

The suspicion of congenital hypophosphatasia is frequently raised byte premature falling out of milk teeth. The diagnosis is corrobarated by the characteristic bone deformities, by the high selection of phosphoetanomalin and by the diminished alkaline phosphataze enzyme activity of the serum. The case of a four years old boy patient is reported on.

Thyroid hormones and thyroglobulin autoantibodies in insulin dependent diabetes mellitus.

Serum T4, FT4, T3, and TSH were measured in a group of children with insulin dependent diabetes mellitus and a control group. In the insulin dependent diabetes mellitus group, serum T3 concentration was significantly lower than the control values. Serum T4, FT4 and TSH level did not differ. The difference in serum T3 concentration was significant between diabetic children with good or poor control. Thyroglobulin antibodies were investigated in diabetic children by Serono's "hTg antibodies" kit. Thyroglobulin antibodies were present in 14.5%. TSH concentration did not differ in antibody positive and negative cases, but one child with diabetes had evidence of moderately impaired thyroid reserve.

Influence of anticonvulsant drugs on thyroid hormones in epileptic children.

Thyroid function tests were studied in epileptic children undergoing long-term anticonvulsive therapy with phenytoin, primidone or mephenytoin. Serum T4 was decreased in all three treated groups, serum T3 was diminished only in those treated with phenytoin or primidone. FT4 was also significantly decreased while serum TSH and TBG were not affected in the treated patients. The effect of anticonvulsant drugs on thyroid hormone catabolism and peripheral conversion of T4 seems to be important in these alterations.