Pentti Lautala

Serum Insulin and Other Cardiovascular Risk Indicators in Children, Adolescents and Young Adults

We wanted to determine the levels of fasting serum insulin during growth, the tracking of serum insulin, and the correlation of serum insulin with other coronary heart disease risk indicators in children and young adults. In 1986 2433 subjects, aged nine to 24 were studied, and insulin data were available from the same population in 1980 and 1983. Serum insulin levels showed a peak during puberty in both sexes and the decline in insulin continued after the age of 21. Tracking of serum insulin was only moderate, especially in females and young boys. Serum insulin correlated positively with body mass index, concentrations of serum triglycerides, and blood pressure, and inversely with the concentration of high density lipoprotein cholesterol. High triglycerides, high systolic blood pressure, and low level of high density lipoprotein cholesterol clustered among subjects within the highest insulin quartile. Our results suggest that the insulin resistance phenomenon, caused mainly by obesity and leading to unfavourable levels of other coronary heart disease risk indicators, is already developing in children and young adults. This suggests that preventing obesity in early life is important.

Antipyretic agents for preventing recurrences of febrile seizures: randomized controlled trial.

OBJECTIVE To evaluate the efficacy of different antipyretic agents and their highest recommended doses for preventing febrile seizures. DESIGN Randomized, placebo-controlled, double-blind trial. SETTING Five hospitals, each working as the only pediatric hospital in its region. PARTICIPANTS A total of 231 children who experienced their first febrile seizure between January 1, 1997, and December 31, 2003. The children were observed for 2 years. INTERVENTIONS All febrile episodes during follow-up were treated first with either rectal diclofenac or placebo. After 8 hours, treatment was continued with oral ibuprofen, acetaminophen, or placebo. MAIN OUTCOME MEASURE Recurrence of febrile seizures. RESULTS The children experienced 851 febrile episodes, and 89 of these included a febrile seizure. Febrile seizure recurrences occurred in 54 of the 231 children (23.4%). There were no significant differences between the groups in the main measure of effect, and the effect estimates were similar, as the rate was 23.4% (46 of 197) in those receiving antipyretic agents and 23.5% (8 of 34) in those receiving placebo (difference, 0.2; 95% confidence interval, -12.8 to 17.6; P = .99). Fever was significantly higher during the episodes with seizure than in those without seizure (39.7 degrees C vs 38.9 degrees C; difference, 0.7 degrees C; 95% confidence interval, -0.9 degrees C to -0.6 degrees C; P < .001), and this phenomenon was independent of the medication given. CONCLUSIONS Antipyretic agents are ineffective for the prevention of recurrences of febrile seizures and for the lowering of body temperature in patients with a febrile episode that leads to a recurrent febrile seizure.

Effect of Once-a-Week Training Program on Physical Fitness and Metabolic Control in Children With IDDM

To examine whether a physical activity program could improve physical fitness and glycemic control, 32 children and adolescents with insulin-dependent diabetes mellitus (IDDM) were examined before the program and 3 mo later. Fifty percent of the subjects (n = 16) participated in the training for 1 h/wk (exercise group), whereas the remaining subjects were engaged in nonphysical activities for an equal amount of time (nonexercise group). Age of the subjects ranged from 8.2 to 16.9 yr, (mean 11.9 yr), with mean duration of diabetes 0.6-13.1 yr (5.2 yr). During the 3-mo program peak oxygen consumption (Vo2) rose from 40.0 to 43.8 ml · min-1 · m-2 (P < .01) in the exercise group but only by 1.3 ml · min-1 · m-2 in the nonexercise group (NS). Metabolic control did not improve in either group, with glycosylated hemoglobin level rising from 9.8 to 10.5% (P < .01) in the exercise group and from 9.4 to 9.7% (NS) in the control group. When subjects were stratified according to their participation, metabolic control was significantly better among diabetic subjects participating frequently (5:11 of 13 sessions) than among those participating infrequently (<11 of 13 sessions), regardless of the type of activity. It was concluded that a training program of 1 h/wk for 3 mo does improve physical fitness but not the metabolic control of diabetes. On the other hand, glycemic control appears to be best among diabetic subjects who are motivated to participate in any kind of program related to the treatment of their disease.

Atherosclerosis precursors in Finnish children and adolescents. VII. Serum immunoreactive insulin

ABSTRACT. In the Finnish Multicentre Study of the risk factors of coronary heart disease serum immunoreactive insulin (IRI) was measured in 3,486 children and adolescents aged 3–18 years. Serum IRI increased with age till the age of 15 years in both sexes. The increase in serum IRI levelled off with the progression of pÜbertal development. Serum IRI levels were higher in girls than in boys from the age of 6 years onwards. Comparison of serum IRI gave identical results from eastern and western parts of the country. Serum IRI correlated positively with skinfold thickness, weight, relative weight and body mass index in all age groups except the 3‐year‐old children.

Cardiovascular Risk in Young Finns, Results from the Second Follow-Up Study

A comprehensive study of coronary heart disease (CHD) risk factors and their determinants in children and adolescents in Finland was initiated in the late 1970s. The main cross-sectional study was undertaken in 1980, with 3596 subjects aged from 3 to 18 years participating. The first follow-up study was carried out in 1983, and the second in 1986. The present report describes briefly some findings in 2746 children and young adults, aged 9, 12, 15, 18, 21 and 24 years, participating in 1986. Serum total cholesterol concentrations, mean (SD), ranged between 4.31 (0.73) and 4.91 (0.81) mmol/l in boys, and between 4.73 (0.85) and 5.09 (0.82) mmol/l in girls, respectively. Mean serum cholesterol values had fallen from 1980 to 1986 by 5.4% in such age cohorts, which had been included in all three studies. Fat content in the diet remained unchanged (38 E %), whereas the mean P/S ratio increased from 0.24 in 1980 to 0.31 in 1986. Young Finns from East Finland had a higher somatic risk index than those from West Finland (P greater than 0.001). The clustering of somatic risk factors was stable between 1980 and 1986. Further follow-up of the cohorts will, we hope, provide the tools for implementing primary prevention of CHD in Finland.

Relation of enteroinsular hormones at birth to macrosomia and neonatal hypoglycemia in infants of diabetic mothers

To study the role of enteroinsular hormones in fetal macrosomia and neonatal hypoglycemia in infants of diabetic mothers, we measured plasma concentrations of free and total immunoreactive insulin, C-peptide, pancreatic glucagon, enteroglucagon, and gastric inhibitory polypeptide at birth in 35 IDMs and 35 infants of normal mothers. Twenty fasting adults of normal weight were also studied. Sixteen IDMs were macrosomic at birth; 17 developed neonatal hypoglycemia over the first postnatal hours. The IDMs had ten times higher concentrations of free IRI than the normal infants in cord blood. Free IRI concentrations were related to the severity of maternal diabetes, with the infants of white class D to F mothers having the highest levels. The IDMs with macrosomia had a twofold increase in the concentrations of free IRI when compared with IDMs of normal weight. There was a significant correlation between the birth weight ratio and the concentrations of free IRI. The IDMs who developed neonatal hypoglycemia had considerably higher concentrations of free IRI than did normoglycemic IDMs. The decrease of blood glucose over the first postnatal hours correlated strongly with the free IRI concentrations in the cord blood. The IDMs had a threefold increase of the C-peptide concentrations over those in normal infants. Six IDMs had a molar ratio of C-peptide to free IRI of less than 1. Both the IDMs and normal infants had substantially higher concentrations of enteroglucagon and lower concentrations of GIP than did the fasting adults. Our data provide direct evidence that IDMs are markedly hyperinsulinemic at birth and that ambient hyperinsulinemia plays a crucial role in the development of fetal macrosomia and neonatal hypoglycemia. Moreover, the observed discrepancy in the relative increase of free IRI and C-peptide, combined with the low molar ratio of C-peptide to IRI, suggests a decreased metabolic clearance of insulin or transplacental passage of insulin from the maternal circulation in infants of mothers with insulin-treated diabetes.

Ocular complications in young adults with insulin-dependent diabetes mellitus since childhood.

A cross‐sectional study in 80 insulin‐dependent diabetic patients born 1963–1968 who experienced the onset of diabetes before 15 years of age showed that at a mean age of 21.6 (range 17–25) years and after a mean duration of diabetes of 13.3 (range 6–24) years, 80% of the patients had retinopathy: 70% had background and 10% proliferative changes. Retinopathy correlated with the duration of the diabetes and poor glucose control at 15 years of age but not with the actual level of glycated haemoglobin. The severity of retinopathy was worse in women than in men. One patient (1.2%) was blind. Two patients had had cataract operations and 66% had myopic refraction in one or both eyes. In 61 patients a further period of ophthalmological follow‐up of 3–4 years was included. After 20 years of diabetes, all had retinopathy and 29% had proliferative changes: 33% had received laser treatment after 8–27 (mean 16.1) years of diabetes. Altogether, 2 patients (2.5% of the original series) were blind. For prevention of diabetic retinopathy and blindness, good glucose control from puberty and careful ophthalmological follow‐up after transfer of the patient from paediatric to adult diabetes care play major roles.

Association of recurrent acute otitis media with nasopharynx dimensions in children

The purpose of this study was to evaluate the hypothesis that the nasopharyngeal anatomy has influence in the risk of recurrent acute otitis media (AOM) attacks. We analysed the occurrence of acute otitis media in 238 healthy schoolchildren who were X-rayed for orthodontic purposes. Six measurements reflecting the size and shape of the bony nasopharynx were recorded from lateral cephalograms. The means for almost all the dimensions of the bony nasopharynx measured were smaller in the children with two or more attacks of AOM in their history than in those with no attack or only one attack. Logistic multivariate modelling showed the distance from the posterior nasal spine to the sella-basion line to be a significant risk factor for recurrent otitis media in girls (difference 1.0 mm; 95 per cent confidence interval 0.1-2.0 mm; p = 0.04) and the shape of the nasopharynx (roundness) in boys (difference 1.9 mm; 95 per cent confidence interval 0.1-4.0 mm; p = 0.01). Measuring the nasopharyngeal bony dimensions may help to identify those children with a risk of recurrent otitis media, at whom prophylactic therapies should be targeted.

Social maturation in juvenile onset diabetes.

We re‐examined a group of 82 (36F, 46M) patients with juvenile onset diabetes at the age of 19–25 years and compared their social outcome in early adulthood with that of a group of 211 randomly selected controls. Their basic school achievements and vocational or higher education were covered in detail in an interview which also included data on their employment status. Various descriptors of social situation and social maturation assessed in a separate interview formed a social maturation index. Relations between factors probably affecting social maturation and this index were analysed. The average marks scored by the diabetics in Finnish comprehensive schools were significantly lower than those of the controls. High school, vocational and commercial schools were discontinued more often by the patient group. Diabetics (27%) and controls (35%) continued their studies equally often in various vocational high schools or universities. Presently, 17% of the diabetics and 11% of the controls had no vocational education or were not on their way to gaining it. Working experience, employment status and unemployment were similar in both groups, but diabetics were more often employed in public service and commerce. At the time of the study the diabetics were significantly more often unmarried and living in the same household as their parents compared with the controls. Other parameters also indicated difficulties in the diabetic group in separating from parents. The overall social maturation index showed poor social maturation in diabetics more often than in the controls. Neither social background, education nor sex were related to poor social maturation. It is concluded that having diabetes delays social maturation. The patients showed a more dependent life‐style and more separation problems. These findings indicate that diabetic patients and their parents need more support if they are to achieve normal social development in early adolescence.

Nocturnal release of immunoreactive growth hormone-releasing hormone and growth hormone in normal children.

ABSTRACT: To evaluate the role of growth hormone-releasing hormone (GHRH) in the physiologic release of growth hormone (GH) we studied the nocturnal secretion of immunoreactive GHRH (ir-GHRH) and its relationship to GH release and various stages of sleep in six prepubertal (three boys) and six pubertal children (two boys) with normal stature. Their ages ranged from 8.1 to 14.9 yr and their bone ages from 6.8 to 14.8 yr. Blood was withdrawn continuously between 2200-0600 h at a constant rate of 5 mL/20 min. The EEG was simultaneously registered. The ir-GHRH and GH data were analyzed by a discrete-pulse detection algorithm (Pulsar). The number of nocturnal ir- GHRH pulses varied from 0-8 (median 7) and the number of GH peaks from 2-6 (median 3). Pubertal children had significantly more (p < 0.05) ir-GHRH pulses and the pulse amplitude was higher (p < 0.05) than in the prepubertal children. There were no significant differences in the GH parameters between the two groups. The ir-GHRH peaks were not significantly related to any specific sleep stage. The majority of the GH pulses (71%) were associated with slow wave sleep (p < 0.001). Two-thirds (69%) of the GHRH peaks preceded closely or coincided with GH pulses (p < 0.02). Pubertal subjects had more isolated ir-GHRH peaks than prepubertal children (p < 0.05). We conclude that the nocturnal secretion of ir-GHRH is pulsatile and, assuming that the peripheral plasma concentrations of ir-GHRH reflect its release from the hypothalamus, GHRH appears to play a physiologic role in the regulation of GH secretion. The partial dissociation between ir-GHRH and GH pulses suggests that other factors are also involved in the regulation of episodic GH release and/or that some of the circulating ir-GHRH originates from extrahypothalamic sources. Pubertal children have increased ir-GHRH secretion, the importance of which remains to be defined.