Introduction of continuous glucose monitoring (CGM) is a key factor in decreasing HbA1c in war refugee children with type 1 diabetes.

AIMS: Our aim was to describe the changes in therapy and diabetes control in Ukrainian war refugee children with diabetes (CwD) during the first year of their stay in Czechia. METHODS: A total of 124 CwD (62 male, 62 female) were enrolled into this observational study. Anthropometric, laboratory and diabetes management data were acquired at baseline and at 3 months intervals for 12 months. All CwD were offered a CGM device during their first visit. Generalized Estimating Equation models were fitted in order to estimate the dynamics of studied characteristics. RESULTS: Median baseline HbA1c was 58 mmol/mol (IQR [48; 73]mmol/mol) (7.5 %, IQR[6.5;8.8]%). The HbA1c decreased significantly throughout the course of the study at a pace of - 2.2 mmol/mol (-0.2 %pt.) per visit (P = 0.01, CI[-3.2;-1.1]). The pace of the decrease in the average HbA1c was significantly higher in the group of CwD who received CGM in Czechia than in those who already had it from Ukraine by 2.9 mmol/mol (0.27 %pt.) per visit (P < 0.001, CI [-4.4; -1.3]). CONCLUSIONS: The steepest decrease in HbA1c was observed in CwD with newly initiated CGM underlining its vital role in improving the glucose control of CwD regardless of their background.

Novel glucokinase gene mutation in the first Macedonian family tested for MODY.

We present a boy with mild hyperglycemia detected during an upper respiratory infection. Novel splicing mutation in the intron 1 of the GCK gene (c.45+1G>A) was detected, and was subsequently confirmed in his father. This is the first case of genetically confirmed Macedonian family with MODY.

Substantial proportion of MODY among multiplex families participating in a Type 1 diabetes prediction programme.

AIMS: Patients with maturity-onset diabetes of the young (MODY) might be over-represented in families with histories of Type 1 diabetes. Our aim was to re-evaluate families participating in the Czech T1D Prediction Programme (PREDIA.CZ) with at least two members affected with diabetes to assess the proportion of MODY among these families and determine its most significant clinical predictors. METHODS: Of the 557 families followed up by the PREDIA.CZ, 53 (9.5%) had two or more family members with diabetes. One proband with diabetes from these families was chosen for direct sequencing of the GCK, HNF1A, HNF4A and INS genes. Non-parametric tests and a linear logistic regression model were used to evaluate differences between MODY and non-MODY families. RESULTS: MODY was genetically diagnosed in 24 of the 53 families with multiple occurrences of diabetes (45%). Mutations were detected most frequently in GCK (58%), followed by HNF1A (38%) and INS (4%). MODY families were more likely to have a parent with diabetes and had a higher proportion of females with diabetes than non-MODY families. Higher age (P < 0.001), a lower level of HbA1c (P < 0.001) at clinical onset and at least two generations affected by diabetes were the variables most predictive for probands of MODY families already presenting with diabetes. CONCLUSIONS: A prediction programme for Type 1 diabetes would provide a useful new source of patients with MODY most likely to benefit from an accurate diagnosis. This identification has implications for patient treatment and disease prognosis.

HbA1c-based diabetes diagnosis among patients with glucokinase mutation (GCK-MODY) is affected by a genetic variant of glucose-6-phosphatase (G6PC2).

AIMS: Genetic variation at the rs560887 locus of the glucose-6-phosphatase, catalytic 2 gene (G6PC2) is known to affect regulation of fasting glycaemia. We determined the rs560887 genotype of patients with monogenic diabetes and glucokinase gene mutations (GCK-MODY) and correlated the genotypes with HbA(1c) levels. METHODS: Patients from families with GCK-MODY were recruited from two large cohorts from Poland (n = 128) and the Czech Republic (n = 154). Genotypes at the rs560887 polymorphic site in G6PC2 were examined using real-time quantitative polymerase chain reaction. The effect of rs560887 genotype on age at diagnosis of GCK-MODY and initial HbA(1c) levels were evaluated separately within both cohorts. Following that, a meta-analysis of rs560887 genotype-HbA(1c) associations of both Polish and Czech cohorts was performed to confirm homogeneity of findings and validate cohort-specific results. RESULTS: GG homozygosity at rs560887 was associated with marginally elevated HbA(1c) levels (P = 0.07 in both cohorts). The effects observed in both groups were very homogeneous (Q = 0.18; P = 0.68). Meta-analysis showed that GG homozygosity at rs560887 was associated with mean HbA(1c) levels higher by 2.4 mmol/mol (0.24%), 95% CI 0.5-4.4 mmol/mol (0.05-0.44%) than in individuals with other genotypes. Additionally, meta-analysis of both cohorts showed that GG homozygous individuals had higher odds of reaching the 48 mmol/mol (6.5%) diagnostic threshold of diabetes; (odds ratio 1.90; 95% CI 1.07-3.36; P = 0.03). No such effects were observed for age at diagnosis of diabetes. CONCLUSIONS: Variation at the rs560887 locus of G6PC2 is associated with worse glycated haemoglobin levels in individuals with GCK mutations; GG homozygotes are more likely to meet diagnostic criteria for diabetes based on HbA(1c) level.

[Ocular manifestations in Turner's syndrome]. / Ocní projevy u Turnerova syndromu.

Turner's syndrome belongs to the most common chromosomal aberrations. It is caused by the deficiency or structural anomaly of one X chromosome, possibly by chromosomal mosaic. In this syndrome, some ocular diseases are more common. During the seven years period, we repeatedly examined 81 girls and women with Turner's syndrome; the range of age was 7-26 years. We observed the eye diseases appearance and their possible association with the karyotype. In these girls, the most common is myopia (29%), item hyperopia (24%), epicanthus (20%), color vision disturbances (17%), amblyopia (12%), strabismus (10%) and ptosis (5%). The color vision disturbances were defined as protanopia in 8.5%, deuteranopia in 3.4% a tritanopia in 5.2%. The occurrence of strabismus and ptosis were higher than in the average population. The total incidence of refractive errors was slightly higher than in normal population, with different incidence according to the karyotype. Hyperopia was found more often in karyotype 45, X (28%), whereas in chromosomal mosaic in 18% only. Inverse proportion was in myopia--in chromosomal mosaic was found in 31% and in karyotype 45, X in 26%. Generally, while comparing the incidence of separate ocular diseases in karyotype 45, X and in chromosomal mosaic, the findings were similar.

[The human lens' transparence changes in children, adolescents, and young adults with diabetes mellitus type I]. / Zmeny transparence cocky u detí, mladistvých a mladých dospelých s diabetes mellitus 1. typu.

Authors followed up the changes' development of the human lens' transparence in 213 children and young adult patients with diabetes mellitus type I. As initial changes of the lens' transparence they considered the posterior "Y" suture accentuation, because it was noticed in 44.4 % of lenses during the first 10 years of the metabolic disease duration, in contrast to 28.1 % representation of this dissociation in the control group of patients without diabetes (p = 0.012), and it was always markedly more often in patients with myopia. Substantial changes were detected predominantly during the sixth until the tenth year of duration of the basic disease as fine subcapsular opacities graded as first degree of lens transparency changes in 48 % of eyes. After 10 years of the disease duration, the lenses were never clear. Consequently, the changes in the transparency in the anterior subcapsular layer associated in 18 %. After 15 years of diabetes duration, we detected opacities in the anterior and posterior subcapsular layers of the lenses, graded as second degree of lenses transparence changes in 85 % of eyes. This subjective evaluating of lenses' opacity changes by means of the slit lamp examination was correlated with densitometric examination by means of Pentacam camera in a representative sample of 29 patients. In the first degree of lenses' transparence changes, the posterior subcapsular layer was affected in 50 %, and in the second degree, the opacities in this layer were found practically in 90 % of cases. False positive result in clear lenses or congenital opacities or "Y" suture was not detected. In general, the affected lens transparency did not basically influence the visual acuity and the decrease of contrast sensitivity was not statistically significant (p = 0.34). For the initial change of the lenses' transparency is also determining the patient's age at the onset of the diabetes mellitus type I. The changes are more common if the onset of the disease is after the fifteenth year of age as before that (p = 0.026). The authors also detected sporadic opacities in 4.2 % of eyes, probably of congenital origin (out of them, in two patients there was bilateral finding of the cerulean cataract) without visual acuity decrease.

[Glibenclamide instead of insulin: a new chance for MODY 3 type diabetes patients: case report]. / Glibenklamid místo inzulinu: nová sance pro pacienty s diabetem MODY 3: kazuistika.

MODY 3 belongs to monogenic forms of diabetes mellitus and is caused by monoallelic mutation in gene for transcription factor HNF-1alpha, essential for regulation of beta-cell function. Clinical presentation of MODY 3 is similar to that of type 1 diabetes. Although MODY 3 patients are not threatened by ketoacidosis, tight metabolic control is important for prevention of chronic diabetic complications. In the sibbling pair diabetes was manifested by osmotic symptoms resulting from hyperglycaemia at the age of 18 years (brother) resp. 15 years (sister) and both of them started being treated with intensified insulin treatment. Metabolic control of the brother was very tight with HbA1c 3.3 % but frequent hypoglycaemias occured. On the contrary metabolic control of the sister was very poor due to her non-compliance (HbA1c 10.9 %, IFCC). Molecular-genetic testing proved HNF-1alpha gene mutation (Arg200Gly). In accordance with the references treatment with sulphonylurea derivate glibenclamide was initiated [at the doses 1.25 (brother) resp. 7.5 (sister) mg/day] and insulin treatment was discontinued. The treatment change led to better quality of life and metabolic control in both the patients and suprisingly to the lower frequency of the hypoglycaemias in the brother (HbA1c decreased from 3.3 % to 2.8 % in three months in the brother resp. from 10.9 % to 10.0 % in two months in the sister). Molecular-genetic testing enables the change of treatment leading to better quality of life and metabolic control, although its longterm safety and efficacy will have to be confirmed.

Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents.

INTRODUCTION: Randomly estimated fasting hyperglycaemia in an asymptomatic individual may represent the first sign of pancreatic beta-cell dysfunction. OBJECTIVE: We aimed at specifying the genetic aetiology of asymptomatic hyperglycaemia in a cohort of children and adolescents. SUBJECTS AND METHODS: We analysed the aetiological diagnosis in 82 non-obese paediatric subjects (38 males) aged 0.2-18.5 years (median: 13.1) who were referred for elucidation of a randomly found blood glucose level above 5.5 mmol/l. In addition to fasting glycaemia and circulating levels of insulin and C-peptide, the subjects were tested by an oral glucose tolerance test and an intravenous glucose tolerance test and screened for mutations in the genes encoding glucokinase (GCK), HNF-1alpha (TCF1), Kir6.2 (KCNJ11) (if aged <2 years) and HNF-4alpha (HNF4A) (those with a positive family history of diabetes). RESULTS AND DISCUSSION: We identified 35 carriers of GCK mutations causing MODY2, two carriers of TCF1 mutations causing MODY3, one carrier of a HNF4A mutation causing MODY1 and one carrier of a KCNJ11 mutation causing permanent neonatal diabetes mellitus. Of the remaining patients, 11 progressed to type 1 diabetes mellitus (T1DM) and 9 had impaired glucose tolerance or diabetes mellitus of unknown origin. In 23 subjects, an impairment of blood glucose levels was not confirmed. We conclude that 39 of 82 paediatric patients (48%) with randomly found fasting hyperglycaemia suffered from single gene defect conditions, MODY2 being the most prevalent. An additional 11 patients (13%) progressed to overt T1DM. The aetiological diagnosis in asymptomatic hyperglycaemic children and adolescents is a clue to introducing an early and effective therapy or, in MODY2, to preventing any future extensive re-investigations.

[The contrast sensitivity test in early detection of ocular changes in children, teenagers, and young adults with diabetes mellitus type I]. / Test citlivosti na kontrast v casné detekci ocních zmen u detí, dospívajících a mladých dospelých s diabetes mellitus 1. typu.

UNLABELLED: The authors examined repeatedly every year 213 patients (97 boys and young men and 116 girls and young women, age ranged 6-36 years, median: 16.4 years). The diabetes mellitus type I duration at the first eye examination was 0.1 to 26 years (median: 5.9 years), and was diagnosed at the age 2-30 years (median 10.5 years). Changes of the posterior pole and their correlation to functional tests and to metabolic parameters were evaluated in five-years periods since the start of the study (within the fifth year of the study, between years 6-10, 11-15, and over 16 years of the study duration respectively). The beginning changes at the fundus were represented by means of dilatation of the capillaries with their possible obliteration and tortuosity, which was rare (7%) until the 5th year of the disease duration, between 6-10 years it was almost in a half of the patients (43 %), and after 10 years in was present in more than 90% of cases. Changes of the macular structure by means of the irregularity of foveolar reflex and relative retinal thickening without significant macular edema with increased pigmentation of this region appeared rarely after the fifth year (5%) and after 15th year of duration were present in more than two thirds of eyes (65%). Combination of these two findings was considered as diabetic preretinopathy (DpR), and was detected in 9% of eyes until 10 years of duration of diabetes. The number of hard exudates and microaneurysms gradually increased. Signs of non-prolipherative diabetic retinopathy were noticed in 0.5% of cases by means of ophthalmoscopical examination in patients with duration of diabetes type I less than 10 years. After that period, the non-prolipherative diabetic retinopathy was present in 19% of cases, and diabetic preretinopathy in 42%. The contrast sensitivity was examined by means of CSV-1000 instrument in 3, 6, 12 and 18 cycles/degree (c/deg) respectively. Normal values for children 6 years old and older were established in a previous study in a control group of children and teenagers without diabetes and with healthy eyes. In the age range 6 - 10 years the mean threshold values [log] are for: 3 c/deg 1.82; 6 c/deg 2.04; 12 c/deg 1.74; and 18 c/deg 1.29. Since the age of 11 years, normal mean threshold contrast sensitivity values [log] are for: 3 c/deg 1.92; 6 c/deg2.19; 12 c/deg 1.89; and 18 c/deg 1.42. No statistically significant difference was found in respective frequencies at the contrast sensitivity curve formulation. The marginal contrast level with standard deviation less than 0.15 log (range, 0.09 - 0.14), for all spatial frequencies represents for children aged 6 - 10 years the 5th stimulation target, and for those of 11 years of age and older the 6th stimulation target disc of the instrument. The value of pathologically decreased contrast sensitivity increased depending on the duration of the diabetes from 1.5% (up to 5 years of diabetes) to 23% after 15 years of diabetes. The lowest decrease of contrast sensitivity in pathological and border values of space frequencies was found in low-frequency 3 c/deg, which shows the evidence of perifoveolar involvement. No statistical significant difference was found among particular frequencies of low, middle, and higher contrast levels in pathological values of contrast sensitivity, but in case of counting in their border values, the statistical significant difference (p = 0.036) was established between the two frequencies 3 c/deg and 18 c/deg, which is giving the evidence of perifoveolar rather than exactly foveolar changes in scope of diabetes mellitus type I. The total decrease of contrast sensitivity values was determined by the increase of changes' number at the posterior pole by means of diabetic preretinopathy and non-prolipherative diabetic retinopathy mostly after 10 years of diabetes duration. Lowering of the contrast sensitivity by 65% is directly related to already mentioned changes of the macular region structure (MDM) and involvement of the foveola with preserved visual acuity. The decrease of the contrast sensitivity corresponded mostly with the posterior pole finding, and not with the diabetes duration, especially in middle and higher frequencies of 6, 12, and 18 c/deg. Changes in color vision by means of 15 Hue test were found in 7% of followed patients and those were not in direct connection with the disease, but were similar to changes in normal population. The decrease of contrast sensitivity values did not depend on the actual metabolic status of the basic disease (actual blood sugar and Hb A1c levels at the time of the ocular examination), nor with the one year level of compensation of diabetes (level of Hb A1c and microalbuminuria during the one year of the study. CONCLUSION: The contrast sensitivity examination by means of CSV-1000 device was not time consuming, non invasive for the patients and in case of good cooperation revealed the functional insufficiency of the retina, which was the sign of initial diabetic changes in foveolar and perifoveolar region structure.

Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection.

AIMS/HYPOTHESIS: Heterozygous mutations in the gene of the transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha) are considered a rare cause of MODY with only 14 mutations reported to date. The description of the phenotype is limited to single families. We investigated the genetics and phenotype of HNF-4alpha mutations in a large European Caucasian collection. METHODS: HNF-4alpha was sequenced in 48 MODY probands, selected for a phenotype of HNF-1alpha MODY but negative for HNF-1alpha mutations. Clinical characteristics and biochemistry were compared between 54 HNF-4alpha mutation carriers and 32 familial controls from ten newly detected or previously described families. RESULTS: Mutations in HNF-4alpha were found in 14/48 (29%) probands negative for HNF-1alpha mutations. The mutations found included seven novel mutations: S34X, D206Y, E276D, L332P, I314F, L332insCTG and IVS5nt+1G>A. I314F is the first reported de novo HNF-4alpha mutation. The average age of diagnosis was 22.9 years with frequent clinical evidence of sensitivity to sulphonylureas. Beta cell function, but not insulin sensitivity, was reduced in diabetic mutation carriers compared to control subjects (homeostasis model assessment of beta cell function 29% p<0.001 vs controls). HNF-4alpha mutations were associated with lower apolipoprotein A2 (p=0.001), A1 (p=0.04) and total HDL-cholesterol (p=0.02) than in control subjects. However, in contrast to some previous reports, levels of triglycerides and apolipoprotein C3 were normal. CONCLUSIONS/INTERPRETATION: HNF-4alpha mutations are common when no HNF-1alpha mutation is found in strictly defined MODY families. The HNF-4alpha clinical phenotype and beta cell dysfunction are similar to HNF-1alpha MODY and are associated with reduced apolipoprotein A2 levels. We suggest that sequencing of HNF-4alpha should be performed in patients with clinical characteristics of HNF-1alpha MODY in whom mutations in HNF-1alpha are not found.

[Normal course of autoimmune thyroid disease in diabetic children]. / Prirozený prubeh autoimunitního onemocnení stítné zlázy u diabetických detí.

BACKGROUND: Autoimmune thyroid disease (AITD) represents the most frequent associated manifestation of the autoimmune disease in children with Type 1 diabetes mellitus (T1DM). The aim of the study was to evaluate the prevalence and natural course of AITD in unselected cohort of diabetic children. METHODS AND RESULTS: TSH, free thyroxin, thyreoglobulin autoantibodies (Ab-hTG), peroxidase autoantibodies (Ab-TPO) and thyroid sonography were prospectively evaluated (1 to 6 years; 323 patient-years) in 110 patients with T1DM (age 2.1-20.8 years; 60 boys). Mild elevation of Ab-hTG and/or Ab-TPO levels (> 100, < 1000 mIU/l) was found in 19 patients (17%; boys:girls 1:2.2). Out of these, only 2 had increased thyroid volume and/or abnormal echotexture. In 9 of these patients, levels of autoantibodies subsequently declined below 100 mIU/l, remained unchanged in 9 patients and only in one case increased over 1000 mIU/l ("benign form" of AITD). All patients remained euthyroid. Severe elevation of Ab-hTG and/or Ab-TPO (> 1000 mIU/l) was found in 12 patients (11%; boys:girls 1:1). Out of these, eight had increased thyroid volume and ten had abnormal echotexture. Subclinical hypothyroidism developed within the observation period in nine of them (boys:girls 2:1). CONCLUSIONS: AITD was found in 31 (28%) children and adolescents with T1DM. Whereas mild elevation of Ab-hTG and/or Ab-TPO levels was not accompanied with morphological changes of the thyroid and did not predict functional disorder, severely elevated levels were associated with the early risk of subclinical hypothyroidism.

Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha.

AIMS/HYPOTHESIS: The aim of this study was to examine the prevalence and nature of mutations in HNF4alpha/MODY1, GCK/MODY2 and HNF-1alpha/MODY3 genes in Czech subjects with clinical diagnosis of MODY. METHODS: We studied 61 unrelated index probands of Czech origin (28 males, 33 females) with a clinical diagnosis of MODY and 202 family members. The mean age of probands was 22.7+/-12.0 years (range, 6-62) and the mean age at the first recognition of hyperglycaemia was 14.7+/-6.0 years (range, 1-25). The promotor and coding regions inclusive intron exon boundaries of the HNF-4alpha, GCK and HNF-1alpha genes were examined by PCR-dHPLC (HNF-1alpha and GCK) and direct sequencing. RESULTS: We identified 20 different mutations in the HNF-4alpha, GCK and HNF-1alpha in 29 families (48% of all families studied), giving a relative prevalence of 5% of MODY1, 31% of MODY2 and 11.5% of MODY3 among the Czech kindred with MODY. Three of 3, 10 of 11 and 1 of 6 of the mutations identified in HNF-4alpha, GCK and HNF-1alpha respectively, were new. CONCLUSION/INTERPRETATION: Of the families 48% carried mutations in the MODY1-3 genes and of the identified mutations 70% were new. In 52% of Czech families with clinical characteristics of MODY, no mutations were found in the analysed genes. This finding shows that the majority of MODY mutations in a central European population are local and that other MODY genes could be responsible for autosomal dominant transmission of diabetes mellitus.

IGF-I resistance and Turner's syndrome.

The pathogenesis of growth failure in Turner's syndrome is not clear but might be attributed to a decreased sensitivity to insulin-like growth factor-I (IGF-I) in distinct cell lines or to its reduced autocrine/paracrine action. Growth hormone (GH) therapy leads to increments in IGF-I levels and to growth acceleration. In order to evaluate the pattern of overcoming IGF-I resistance through childhood and adolescence, we measured IGF-I in 78 girls with Turner's syndrome aged 4.6-18.3 years on 160 occasions without or during GH (1 IU/kg/week [0.33 mg/kg/week]) or GH+estradiol (E2) therapy and compared them with local IGF-I standards. In untreated patients, IGF-I levels were low normal (-0.71+/-0.18 SDS, mean +/- SEM). In both GH or GH+E2 treated girls, circulating IGF-I levels were persistently supraphysiological (GH only: +3.61+/-0.23 SDS; GH + estradiol: +3.18+/-0.31 SDS). The age-dependent pattern of IGF-I secretion was conserved but the pubertal increase occurred earlier. The highest standardized IGF-I levels were observed at age 8.5-9.4 years (+6.62+/-1.00 SDS) and 9.5-10.4 years (+5.61+/-1.03 SDS). GH+E2 substitution had no additional effect on circulating IGF-I. We conclude that high IGF-I levels are needed to overcome the IGF-resistance in Turner's syndrome. They reflect the action of GH therapy but not of estrogens. The earlier pubertal increase of IGF-I might be caused by exaggerated adrenal androgens.

Immune system in adults with childhood-onset growth hormone deficiency: effect of growth hormone therapy.

OBJECTIVE: To investigate the impact of growth hormone (GH) therapy in adults with childhood-onset GH deficiency on immune system. METHODS: Ten young GH deficient adults (7 males, age 19-28 years) were treated with recombinant human growth hormone for 6 months. The starting dose was 0.5 IU/m2/day (2 weeks), then it was doubled to 1.0 IU/m2/day. In 5/10 patients, the dose was further increased to 1.5 IU/m2/day at 4 weeks of therapy. Immunological studies were performed before treatment and after 6 weeks, 3 months and 6 months and included humoral (IgG, IgA, IgM, C3, C4 and immune complexes) and cellular parameters (total lymphocyte count and counts of CD3+, CD4+, CD8+ and CD19+ lymphocytes, the CD4+/CD8+ ratio and percentage of CD16+56+ and CD3+DR+). RESULTS: The cellular responses to GH therapy were subtle, but detectable, with the trend to the higher CD4+ and lower CD8+ lymphocytes and maximal changes at 6 months of therapy. They were reflected in CD4/CD8 ratio, which increased from 1.15 +/- 0.10 (mean +/- S.E.; baseline) to 1.37 +/- 0.11 (6 weeks; P < 0.05), 1.24 +/- 0.10 (3 months; n.s.) and to 1.59 +/- 0.20 (6 months; P < 0.05). The response in humoral immunity was characterized by a rapid decrease of circulating immunoglobulins (IgA: 1.40 +/- 0.25 g/l [mean+/-S.E.], baseline; 1.12 +/- 0.19, at 6 weeks; P < 0.05) and C4 (0.25 +/- 0.02 g/l, baseline; 0.19 +/- 0.01, at 6 weeks; P < 0.05) and a tendency to an increase in circulating immune complexes (29.1 +/- 8.1, baseline; 40.3 +/- 7.2, at 6 weeks; n.s.). These observations suggest a temporary immune complex formation after the onset of GH treatment which might play a partial role in developing oedema as a side effect of GH treatment, besides the known effect of GH on water retention. CONCLUSIONS: GH therapy in GH deficient young adults has a measurable effect on the increase of CD4/CD8 ratio and on the formation of immune complexes.