Gestational diabetes and offspring body disproportion.

AIM: It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants. METHODS: Birth characteristics of 884,267 infants of non-diabetic mothers and 7817 of mothers with GDM were analysed. LGA was defined as birth weight or birth length >2 standard deviation scores for gestational age. Multiple logistic regression analysis was performed. RESULTS: The odds ratio (OR) for a woman with GDM to give birth to an LGA infant that was heavy alone was four times increased (OR: 3.71, 95% CI: 3.41-4.04). Furthermore, in the population of mothers giving birth to LGA infants, the proportion heavy alone was 68% in the group of women with GDM compared with 64.4% in the group of non-diabetic women. The risks were independent of gender of the foetus. CONCLUSION: Women with GDM have an almost four times higher risk of delivering an LGA infant that is heavy alone. The noted disproportion between weight and length in infants of such mothers may have an impact on the risk of later obesity.

Preterm appropriate for gestational age infants: size at birth explains subsequent growth.

AIM: The aim was to evaluate growth and breastfeeding up to 18 months corrected age (CA) among preterm appropriate for gestational age (AGA) infants whose mothers initiated breastfeeding during the infants' hospital stay. METHODS: One hundred and twenty-seven preterm AGA infants with a median birth weight of 2320 (769-3250) g and gestational age 34.29 (25.00-35.86) weeks were evaluated up to a CA of 18 months. A retrospective, descriptive and comparative design was used. Data were obtained by chart review of hospital medical records and a questionnaire completed by the mothers. RESULTS: The changes in standard deviation scores (SDS) during the infants' hospital stay were -0.9 for weight, -0.3 for length and -0.5 for head circumference (HC). Infants with higher SDS at birth showed more negative changes from birth to discharge. Median increments in SDS from discharge to a CA of 2 months were as high as, or higher than, the loss from birth to discharge. CONCLUSION: Preterm AGA infants with higher SDS for weight, length and HC at birth are at higher risk of inadequate growth during their hospital stay.

A unifying hypothesis on the development of type 1 diabetes and celiac disease: gluten consumption may be a shared causative factor.

This paper presents a hypothesis of the aetiology of the increasing incidence of type 1 diabetes (T1D). This together with the global increased incidence of celiac disease (CD) and that these increases cannot be explained by genetic factors suggest a common environmental factor for these two diseases. Even though enterovirus (EV) infections are believed to trigger T1D and gluten is the trigger of CD, the increasing intake of gluten containing products all over the world could be the trigger for both diseases directly and indirectly. It has been shown that the duration of exposure to gluten is related to the prevalence of T1D. It has also been shown that T1D patients at onset have an inflammatory reaction in the gut. Hence, early diagnose of CD followed by elimination of dietary gluten will lead to a decreased incidence of T1D.

Can bone age determination provide criteria for growth hormone treatment in adopted girls with early puberty?

In treatment of idiopathic central precocious puberty, GnRH analogues (GnRHa) have been accepted as the treatment of choice. Since growth velocity may be impaired with GnRHa treatment growth hormone (GH) treatment has been added in clinical trials. Recently, a study followed adopted girls with early or precocious puberty on GnRHa or combined GnRHa and GH treatment to final height. It was found that final height was significantly higher in the combined treatment group, although the difference was small. It was seen that patients that were extremely short at arrival and short at start of treatment seemed to be candidates for combined treatment. We have now analysed the data in order to define criteria for the sub-group in need of combined GnRHa-GH treatment in order to achieve normal final height, i.e. above -2 SDS. Bone ages of 46 patients at start of treatment, randomized to either GnRHa treatment or GnRHa treatment combined with GH, were examined blindly by the same radiologist and the PAH calculated. The methods according to Greulich-Pyle / Bayley-Pinneau (GP/BP) and Tanner-Whitehouse (TW2) were used. Predictions versus final height data were analysed. The accuracy of FH prediction was greatest for GnRHa treated group using the GP/BP method. The GP/BP method gave useful cut off limits for when combined treatment was necessary to possibly achieve normal height. If pre-treatment GP/PAH was > 157cm, the patients attained normal height with GnRHa treatment only. Ten out of 13 (77%) such girls could be correctly identified. Using TW2 with a cut off of 164 cm, 9 out of 13 could be selected. Using a multi regression equation of best fit the number of correctly selected cases for GnRHa treatment only, could not be further increased in this group. We conclude that bone age determination and adult height prediction with the Greulich-Pyle/Bayley-Pinneau method, provides useful criteria for selecting the subgroup of adopted girls with early puberty where combined treatment with GnRHa and GH is not necessary to reach normal final height.

Growth and breastfeeding among low birth weight infants fed with or without protein enrichment of human milk.

The effect of protein enrichment of mother's milk on growth of low birthweight infants needs further exploration in order to optimize feeding strategies. The aim of this study was to describe feeding and growth of infants weighing <1,900 g at birth, up to a corrected age of 18 months, with or without protein-enriched breastmilk. A retrospective, descriptive, non-experimental design was used to describe the growth of 52 low birthweight infants. Data on their growth and feeding were collected from medical records at hospitals and child health care clinics. Despite more severe morbidity, the infants given protein-enriched milk showed similar growth as the other study infants. Standard deviation score for length at birth correlated positively with delta standard deviation score for length, from discharge to 12 and from discharge to 18 months corrected age. Duration of 'full' breastfeeding had a significant impact on subsequent improvement in SDS for weight. At discharge a smaller proportion of singletons fed with protein enriched milk were breastfed 'fully'. Infants who established breastfeeding at an early post-menstrual age were born with more optimal weight standard deviation score and had a better weight gain after discharge. We conclude that protein-enriched breast milk enables low birthweight infants requiring especially intensive care to attain growth at discharge comparable to that of healthier infants not given enriched milk. Low standard deviation score for length at birth may predict poor growth after discharge. However duration of 'full' breastfeeding had a significant impact on subsequent improvement in SDS for weight. Therefore it is important that mothers of LBW infants are given sufficient support of lactation and breastfeeding.

Lack of cutaneous hyperemia in response to insulin-induced hypoglycemia in IDDM.

Cutaneous blood flow was measured with the laser Doppler technique and by recording cutaneous O2 tension on the forearm and forehead in nine young adult patients with insulin-dependent diabetes mellitus (IDDM) and nine sex- and age-matched healthy control subjects after induction of hypoglycemia. In the healthy subjects, cutaneous blood flow measured with the laser Doppler technique was increased by 120 +/- 26% in the forehead (P less than 0.01) and 196 +/- 50% in the forearm (P less than 0.01) at the glucose nadir (blood glucose 1.8 +/- 0.2 mM) compared with basal blood flow. In contrast, in diabetic patients, cutaneous blood flow was unchanged. The corresponding changes, at the glucose nadir, with cutaneous O2 tension recordings were 286 +/- 131% (P less than 0.05) in control subjects and -22 +/- 15% (NS) in diabetic patients. An impairment of sympathetic nervous function, not detectable by simple cardiovascular tests, could be responsible for the lack of cutaneous hyperemia and sweating and could contribute to unawareness of hypoglycemia in diabetic patients.

Epidemiology of childhood type I diabetes in Sudan, 1987-1990.

OBJECTIVE: To determine the incidence of type I diabetes in children 0-14 yr of age in Khartoum, Sudan. RESEARCH DESIGN AND METHODS: Prospective registration of newly diagnosed patients in a hospital-based registry with independent validation of completeness of case ascertainment. Eligible patients were Sudanese children < 15 yr of age, who developed type I diabetes during the period 1 January 1987 through 31 December 1990, and who were living in Khartoum city at the time of diagnosis. The denominator is the stable childhood population of Khartoum city, as estimated by the National Bureau of Statistics. RESULTS: In 4 yr, 239 cases were notified in the primary source and 268 in the secondary source. Some 196 patients were registered in both sources. Using the capture-recapture method to correct for underascertainment, the estimated total number of cases was 327, and the overall degree of ascertainment was 95%. The incidence of type I diabetes in children 0-14 yr of age increased from 5.9/10(5) in 1987 to 10.1/10(5) in 1990 (P < 0.001). Girls exhibited slightly higher incidence rates than boys in the 10-14-yr age-group throughout the 4 yr, but the differences were not statistically significant. The age distribution at onset was bimodal with a clear peak at age 12 yr in girls and age 14 yr in boys and another smaller peak at age 7 yr in both sexes. The number of new cases was markedly higher in the cooler months of the year, with a peak in January and a nadir in June (P < 0.01). This trend was consistent over the period of observation. CONCLUSIONS: Childhood diabetes is increasing in Sudan. Our incidence figures are higher than those reported from other Arab countries and is similar to reports from France and Italy.

Prevalence of IDDM in schoolchildren in Khartoum, Sudan.

The prevalence of insulin-dependent diabetes mellitus (IDDM) in 42,981 schoolchildren (aged 7-14 yr) in Khartoum, Sudan, was determined. With the 1985 World Health Organization revised criteria for diagnosis and classification of diabetes mellitus, the overall crude prevalence rate of IDDM was 0.95/1000 in the age groups studied. This figure is thought to reflect the minimum prevalence of IDDM in that population, because there is an inherent tendency in the method of screening used toward underestimating the true prevalence rate. The prevalence of IDDM was found to increase significantly with age and was slightly higher in girls than boys, but this was not statistically significant. Of 41 children with IDDM detected in the survey, 7 were not known to have IDDM before but were showing suggestive symptoms at the time of the study. This study showed that IDDM in childhood is not rare in Sudan and that probably a substantial number of undiagnosed cases exist.

Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.

The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.

Linear catch-up growth does not increase the risk of elevated blood pressure and reduces the risk of overweight in males.

OBJECTIVES: To analyse if size at birth is associated with blood pressure and body mass index (BMI) at conscription in males, and if linear catch-up growth in height modifies these associations. DESIGN: A population-based cohort study of 276 033 single-born males aged 17-24. Information from the Swedish Birth Register was individually linked to the Swedish Conscript Register. Systolic blood pressure was standardized for final height. RESULTS: Compared to males not being small for gestational age at birth, males being light for gestational age [<-2 standard deviation scores (SDS)] were at increased risk of high systolic blood pressure [odds ratio (OR) 1.33; 95% confidence intervals (CI) 1.20-1.46], and a short adult stature was associated with a further increased risk [OR 1.65 (CI 1.13-2.40)]. Being born short for gestational age (<-2 SDS) was associated with a slightly increased risk of high systolic blood pressure [OR 1.16 (CI 1.04-1.29)], and linear catch-up growth in height did not increase this risk. Males born short for gestational age, who also were short at conscription, had an increased risk of a high BMI [OR 1.65 (CI 1.25-2.19)]. CONCLUSIONS: Males born light for gestational age have an increased risk of high systolic blood pressure, especially if they end up with short adult stature. Being born short for gestational age is associated with a slightly increased risk of high systolic blood pressure, and catch-up growth is not associated with a further risk. Lack of catch-up growth is, among males born short for gestational age, associated with an increased risk of overweight.

Sleep of children with enuresis: a polysomnographic study.

OBJECTIVE: To evaluate relationships between bladder voiding and sleep in children with enuresis. METHODS: Polysomnographic recordings were obtained from 25 children, aged 7 to 17 years, with monosymptomatic nocturnal enuresis. During 52 recorded nights, 37 enuretic events were detected. Responders (n = 7) and nonresponders (n = 16) to desmopressin treatment were compared. RESULTS: The mean latency between sleep onset and the first bladder voiding was 3 hours 20 minutes (SD = 2 hours 5 minutes). The number of voidings were 19, 7, 10, and 1 occurring during stages 2, 3, and 4, and rapid-eye movement sleep, respectively. Desmopressin responders were found to void during the early or late part of the night, whereas the voidings of the nonresponders were dispersed evenly throughout the night (chi2 = 8.09). CONCLUSIONS: The enuretic event is a predominantly non-rapid eye movement sleep phenomenon. Responders and nonresponders to desmopressin treatment void during different parts of the night.

Graves' disease in children and adolescents. Late results of surgical treatment.

All children and adolescents with Graves' disease in the county of Uppsala (catchment area population 250,000) treated between 1970 and 1994 were evaluated in a retrospective study. The material comprised 31 patients with a mean age of 11 years (range 4-16), 29 (94%) of whom were girls, and four (13%) of the patients had Down's syndrome. Treatment was primarily conservative and surgery was considered if prolonged medical treatment failed. Lasting remission after antithyroid drug therapy (median 6.5 years; range 4.5-8 years) was noted in 6/31 patients (19%), three (10%) of whom subsequently developed hypothyroidism. Twenty-four of the remaining patients (77%) ultimately underwent subtotal (N = 20) or total thyroidectomy (N = 4) after experiencing one or more episodes of recurrent hyperthyroidism during medical treatment (median 6 years; range 0.5-11 years). After surgery one patient developed permanent hypocalcemia requiring low-dose vitamin D supplementation. During a postoperative follow-up period of 12.2 years ( median; range 1-17 years), there were two cases of recurrent thyrotoxicosis, 1 and 10 years after surgery. The results underline that gender and Down's syndrome are risk factors of juvenile Graves' disease and that the disorder often is difficult to control by long-term medical therapy. In such cases thyroid surgery offers a safe and prompt reversal of the thyrotoxicosis. A proportion of the patients may ultimately develop hypothyroidism, substantiating a need for long-term follow-up of persons afflicted with Graves' disease early in life.

Growth hormone therapy in young children with Down syndrome and a clinical comparison of Down and Prader-Willi syndromes.

The genetic disorders Prader-Willi syndrome and Down syndrome have a number of features in common, for example, both growth and mental retardation. Growth hormone (GH) treatment is becoming part of the clinical management of children with Prader-Willi syndrome, but in children with Down syndrome, such therapy is still on a research level. In this review, we compare the clinical phenotypes of the two syndromes, and report the effects of long-term GH treatment on the linear growth and psychomotor development of 15 young children with Down syndrome (mean age at start of treatment, 7.4 months). The mean height of the treated children with Down syndrome increased significantly from -1.8 to -0.8 SDS (Swedish standard) during the 3 years of GH therapy (P < 0.001). The mean height of a corresponding control group fell from -1.7 to -2.2 SDS. After the cessation of treatment, growth velocity declined in the treated group. Growth of the head did not increase during GH treatment. There was no effect on mental or gross-motor development, although some improvement in fine-motor development was noted in the GH-treated group (P < 0.01). At present, treatment with GH is not recommended in children with Down syndrome who have not been diagnosed with GH deficiency. Long-term studies with an emphasis also on the metabolic effects of GH therapy are necessary before routine treatment can be considered in such children.

Magnesium and insulin-dependent diabetes mellitus.

There is accumulating evidence that the changes which occur in the metabolism of some micronutrients in diabetes mellitus might have a specific role in the pathogenesis and complications of this disease. Magnesium deficiency is the most evident disturbance of metal metabolism in insulin-dependent diabetes mellitus. Hypomagnesemia has been linked both to the acute metabolic and late chronic complication of diabetes. Of particular concern, is the association between hypomagnesemia and ischemic heart disease and severe retinopathy in humans with diabetes mellitus. Appropriate magnesium supplementation might prove beneficial in normalizing the low plasma and tissue magnesium levels and prevent or retard the development of vascular complications in diabetic patients. However, well designed and documented experiments need to be performed before the rationales for such therapy are well established.

Islet-cell antibodies and endogenous insulin secretion in Sudanese diabetic children.

Cytoplasmic islet-cell antibodies (ICA) and endogenous insulin secretion were studied in 46 Sudanese children (mean age 11.6 years) with newly diagnosed insulin-dependent diabetes mellitus (IDDM). Islet-cell antibodies were detected both by the indirect immunofluorescence (IF) and complement fixation (CF) methods. Endogenous insulin levels were measured as C-peptide concentration using radio-immunoassays. The degree of metabolic control of diabetics was judged by the presence of diabetic ketoacidosis (DKA) at onset, glycated haemoglobin (HbA1c) level and insulin requirement, expressed as dose per kg body weight per day, at the time of presentation. Twenty-nine patients (63%) had either IF-ICA or CF-ICA or both in their sera. These figures are significantly higher than those reported for African populations. Islet-cell antibody positive patients had significantly lower C-peptide concentration, higher HbA1c level, higher insulin requirement and higher prevalence of ketoacidosis at presentation. Furthermore, the C-peptide levels were higher in CF-ICA positive patients than in subjects who showed only IF-ICA positivity. Our findings show a clear association between ICA and severity of diabetes at clinical onset and also suggest that the presence of CF-ICA at or shortly after diagnosis of IDDM is indicative of preservation of some functioning beta-cell mass.

The possible role of Coxsackie A and echo viruses in the pathogenesis of type I diabetes mellitus studied by IgM analysis.

IgM antibodies to Coxsackie B virus (CBV) have recently been observed in the serum of a relatively high proportion of children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). In the present study, 108 IDDM patients below the age of 15 years, diagnosed during the period 1976 to 1985, were investigated at the onset of their disease by mu-antibody-capture radioimmunoassay (RIA) of IgM against seven different enterovirus antigens, namely virions of CBV serotypes 1-5 (CBV 1-5) and procapsids of CBV 3 and CBV 5. As has been shown the RIAs with virions give type-specific or narrow type-specific reactions, whereas procapsids react with IgM against both homotypic and heterotypic enteroviruses. The annual frequency of IgM against virions varied between 15 and 76% (mean 38%). IgM against CBV3 and CBV2 predominated, but IgM against the other serotypes was also observed. When procapsids were used as antigen, the frequency of IgM varied between 11 and 86% (mean 63%). With virions and procapsids, the corresponding variation was 44-100% (mean 70%). The total number of patients exhibiting virion-IgM was 41, whereas procapsid-IgM alone [indicating an infection with Coxsackie A virus (CAV) and/or echo virus (EV)] was detected in 36 patients. For 2 of the years, samples of serum from control groups were included. These showed a significantly lower frequency of IgM in both the virion and the procapsid RIAs. It is concluded that not only infection with CBV but also that with other enteroviruses, such as CAV and/or EV, may be involved in the pathogenesis of IDDM in children.

Impaired cutaneous reactive hyperaemia during hypoglycaemia in young insulin-dependent diabetic patients and healthy controls.

The aim of the present study was to compare the cutaneous postischaemic hyperaemic response in young insulin-dependent diabetic patients and healthy subjects during normoglycaemia, acute insulin-induced hypoglycaemia and in the posthypoglycaemic state. After a night of normoglycaemia the cutaneous postischaemic hyperaemic response in the forearm skin, measured by the transcutaneous PO2 method, was the same in both groups. A reduction of the maximal postischaemic vasodilatory response was observed in diabetic patients from 2.4 +/- 0.3 to 2.0 +/- 0.2 kPa (P less than 0.05) and in control subjects from 2.7 +/- 0.3 to 1.8 +/- 0.2 kPa (P less than 0.02) during insulin-induced hypoglycaemia (plasma glucose less than 2 mmol/l). Complete recovery of the vasodilatory response occurred in subjects in the posthypoglycaemic state. We conclude that hypoglycaemia induced a transient reduction of the vasodilatory response, which was rapidly reversed after glucose counter-regulation, in both diabetic patients and healthy controls. Thus, the prevailing blood glucose concentration must be taken into account when the postischaemic vasodilatory response is investigated in diabetic patients.

Effects and interactions of oxygen and prostaglandins on the tone of the isolated human umbilical artery.

Prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) were found to be equipotent contractors of the isolated human umbilical artery (HUA) in the concentration range 0.2-40 mug/ml. Prostaglandin E1 (PGE1) relaxed HUA at 0.1-3.0 mug/ml, whereas at 10-50 mug/ml contraction occurred. PGE2 was significantly more potent at a PO2 of 102 mmHg than at 27, 48 and above 400 mmHg. An increase in PO2 per se (27- greater than 400 mmHg) resulted occasionally in minor increases in the tone of the HUA. Such effects of oxygen had a lag period of 10-15 min. It is suggested that an increased formation of prostaglandins in the umbilical artery at birth is a more likely cause of the closure of the vessel than an increase in PO2.

Increased platelet volume in manifest diabetic rats.

Platelet function, evaluated as in vitro aggregability, has been reported to be disturbed in diabetes, both in humans and animals. Platelet number and mean volume greatly influence these aggregation tests. The present study was designed to evaluate the impact of two different degrees of experimentally induced glucose intolerance on platelet number and mean volume. For this purpose, we used manifest diabetic and chemically diabetic rats. In the control group, the female rats showed a significantly lower number of platelets compared to the males. The chemically diabetic rats exhibited a tendency towards increased mean platelet volume, whereas the platelet volume of the manifest diabetic females was significantly greater than all other groups. This increase was found to be mainly due to a general shift towards larger volumes of the individual platelets of the manifest diabetic females. It is suggested, that the enlargement of the mean platelet volume induced by increased severity of the diabetic state may reflect decreased mean age of the circulating platelets. This implies shorter survival time and an increased turnover of the platelet population in diabetes mellitus.

Cord blood platelet aggregation; quality control by a two-sample technique.

Two blood samples were taken from the cords at 17 normal deliveries 2-4 min and 5-8 min after birth, respectively. The difference in platelet count between early and late samples in platelet-rich plasma was less than 5% in nine cords (Group A), and greater in eight cords (Group B). Platelet aggregation studies on the early and the late blood samples showed consistent results within each cord in Group A but not in Group B. The correlations between the responses were high for Group A. The aggregation responses were also slightly but significantly higher in the late samples in this group (p less than 0.01 in Group A; n.s. in Group B). The differences between responses in early and late blood samples could not be explained by acid-base dissimilarities. The variability in cord blood platelet aggregation results can be greatly reduced by platelet counting in PRP of two independent blood samples, accepting only samples with concordant platelet counts (less than 5% difference).