Biomedical subjects
Publications and source records attributed to Angelika Mohn.
We studied the evolution of beta-cell function in 32 children treated for acute lymphoblastic leukemia (ALL) through a long-term follow-up after completion of therapy. Our results show that although alterations of the glucose metabolism persists after stop-therapy they are reversible with time.
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OBJECTIVES: To investigate the relationship between ambulatory blood pressure (ABPM) parameters and insulin resistance in obese children. METHODS: A population of 56 obese prepubertal children was recruited for the study. They underwent ABPM, an oral glucose tolerance test and complete physical examination, including adiposity indexes such as body mass index (BMI), skinfolds, waist-to-hip ratio (WHR) and fat mass. RESULTS: The standard deviation score for BMI was significantly correlated with 24-h systolic blood pressure (SBP) (r = 0.30; P = 0.02) and diastolic blood pressure (DBP) (r = 0.29; P = 0.03), daytime SBP and DBP (r = 0.28; P = 0.04 and r = 0.32; P = 0.02), night-time SBP and DBP (r = 0.32; P = 0.01 and r = 0.27; P = 0.04). Fat mass was correlated with 24-h SBP (r = 0.46; P = 0.005), daytime SBP (r = 0.40; P = 0.01) and night-time SBP (r = 0.49; P = 0.03). No correlations were found between ABPM parameters and WHR. Furthermore, significant correlations were found between insulin resistance indexes, such as the homeostasis model assessment of insulin resistance and quantitative insulin-sensitivity check index, and 24-h DBP (r = 0.34; P = 0.01 and r = -0.29; P = 0.03), daytime DBP (r = 0.35; P = 0.009 and r = -0.34; P = 0.01) and daytime SBP (r = 0.32; P = 0.02 and r = -0.27; P = 0.04). Only 24-h and daytime DBP remained correlated with insulin resistance after adjustment for obesity. The analysis of the circadian rhythm of blood pressure revealed that 24 out the 56 children were non-dippers. CONCLUSIONS: The results of the present study indicate that adiposity and insulin resistance have an important role in influencing blood pressure in obese children, and also show a high prevalence of non-dipping phenomenon. This is of particular relevance because blood pressure tracks from childhood into adulthood and an already early-life high blood pressure is associated with an increased cardiovascular risk.
OBJECTIVE: The aim of the present study was to evaluate serum and urinary nitric oxide (NO) concentrations in children and adolescents with diabetes compared with age-matched healthy control subjects to find out whether Doppler ultrasonography could be used to detect changes in renal resistive indexes (RIs) in children with diabetes and to assess whether there are correlations between these parameters and NO excretion. RESEARCH DESIGN AND METHODS: We studied 42 children with type 1 diabetes and 41 matched healthy control subjects, both divided into prepubertal or pubertal children. Serum and urinary nitrite and nitrate (NO2-+NO3-) concentrations were evaluated as an index of NO production. Doppler ultrasonographic registration of intrarenal RI was performed. RESULTS: Compared with healthy control subjects, children with diabetes had significantly increased concentrations of serum (30.26 +/- 6.52 vs. 24.47 +/- 7.27 mmol/l, P = 0.001) and urinary NO2-+NO3- (345.07 +/- 151.35 vs. 245.86 +/- 80.25 mmol/l, P = 0.002); the same was true for Doppler RI values (0.64 +/- 0.03 vs. 0.60 +/- 0.04, P = 0.035). This occurs in both prepubertal and the pubertal children. A significant positive correlation was found between serum and urinary NO2-+NO3- levels (P = 0.002, r = 0.374). Serum NO2-+NO3- concentrations also correlated positively with Doppler RI (P = 0.032, r = 0.262) and HbA1c (A1C) (P = 0.004, r = 0.329); urinary NO2-+NO3- concentrations correlated positively with A1C (P = 0.001, r = 0.394). Doppler RI correlated positively with A1C (P = 0.000, r = 0.424). CONCLUSIONS: This study demonstrates that in children with diabetes, chronic hyperglycemia may act through a mechanism that involves increased NO production and/or action and contributes to generating intrarenal hemodynamic abnormalities, which are detectable by Doppler ultrasonography even in early diabetic nephropathy.
Oxidant-antioxidant status was investigated in a group of severely obese prepubertal children in comparison with healthy subjects and in relation to a dietary restriction-weight loss program. All subjects underwent anthropometric measurements and determination of lipid profile, lag phase, malondialdehyde (MDA), and vitamin E. Compared with controls, obese children had a significantly higher body mass index (BMI) (28.97 +/- 2.42 vs. 16.03 +/- 1.88 kg/m2; P = 0.0002) and waist-to-hip ratio (WHR) (0.89 +/- 0.03 vs. 0.80 +/- 0.01; P = 0.0004); lag phase and vitamin E levels were significantly decreased [24.05 +/- 16.21 vs. 43.16 +/- 10 min (P = 0.004) and 21.12 +/- 14.96 vs. 35.54 +/- 13.62 micromol/liter (P = 0.02), respectively], whereas MDA was significantly increased (0.90 +/- 0.31 vs. 0.45 +/- 0.24 nmol/mg; P = 0.001). Both lag phase and MDA significantly correlated with BMI [respectively, r = -0.34 (P = 0.004) and r = 0.57 (P = 0.002)] and WHR [respectively, r = -0.63 (P = 0.0001) and r = 0.38 (P = 0.04)]. Oxidant status normalized after 6 months of dietary restriction [lag phase, 59.11 +/- 14.74 min (P = 0.002); MDA, 0.47 +/- 0.09 nmol/mg (P = 0.003)], which was associated with a reduction of BMI (27.34 +/- 1.87 kg/m2; P = 0.003), WHR (0.87 +/- 0.02; P = 0.001), and fat mass (34.49 +/- 2.68%; P = 0.008), but returned to baseline levels together with fatness indexes after another 6 months of free diet. Altered oxidant-antioxidant status is already present in prepubertal severely obese children and is reversible with a dietary restriction-weight loss program, which should be highly encouraged and maintained over time in this age group.
OBJECTIVE: Growth hormone deficiency (GHD) in adults is associated with increased oxidative stress determined by the underlying GH-IGF-1 axis alterations. Despite GHD being a common diagnosis in children with short stature, no data on the oxidant/antioxidant status are available in this age group. This study was designed to detect differences in oxidative stress parameters between prepubertal GH-deficient children and healthy controls. Furthermore, the effect of 12 months of conventional GH replacement (rGH) on oxidant-antioxidant status was evaluated in the GHD group only. PATIENTS: Ten (nine males and one female) prepubertal children (mean age 9.1 +/- 1.3 years) with GHD were recruited and matched for sex and age (9.2 +/- 1.9 years) with 20 healthy controls (18 males and two females). MEASUREMENTS: At study entry, lag phase, an index of susceptibility of low density lipoprotein (LDL) to in vitro oxidation, malondialdehyde (MDA) and vitamin E were measured in all subjects. These parameters were also evaluated in GH-deficient children after 12 months of rGH treatment. RESULTS: The lag phase was significantly decreased in GH-deficient children compared to healthy controls (15.50 +/- 7.4 vs. 43.00 +/- 9.2 min; P = 0.0007), while MDA was significantly increased (1.33 +/- 0.38 vs. 0.46 +/- 0.10 nmol/mg; P = 0.0006). Vitamin E levels were significantly decreased (22.44 +/- 9.57 vs. 35.38 +/- 16.49 micromol/l; P = 0.001). IGF-1 and IGFBP-3 correlated directly to lag phase (r = 0.48; P = 0.01; r = 0.63, P = 0.002, respectively) and to vitamin E (r = 0.59, P = 0.003; r = 0.58, P = 0.006, respectively). By contrast, IGF-1 and IGFBP-3 correlated indirectly to MDA (r = -0.47, P = 0.01; r =-0.65, P = 0.002, respectively). After 1 year of rGH therapy, lag phase (39.32 +/- 15.24 min; P = 0.005) and vitamin E (34.9 +/- 7.7 micromol/l; P = 0.005) increased significantly, while MDA decreased significantly (0.71 +/- 0.42 nmol/mg; P = 0.005), reaching normal levels. CONCLUSIONS: These data show that children with GHD have substantially increased oxidative stress parameters compared to healthy controls and demonstrate a normalization of these parameters after 1 year of rGH therapy.
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OBJECTIVE: Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. The objective of this study was to evaluate the effects of irbesartan, an angiotensin II receptor antagonist, on IAP in adolescents and young adults with type 1 diabetes and early signs of retinopathy and nephropathy. RESEARCH DESIGN AND METHODS: This prospective, matched case-control study was conducted between November 2001 and December 2002 among 14 type 1 diabetic patients with early signs of angiopathy (ages 14-21 years), 11 type 1 diabetic patients without angiopathy (ages 12-22 years), and 10 healthy volunteers (ages 16-22 years). Skin fibroblasts were obtained by skin biopsies from the anterior part of the forearm and cultured in Dulbecco's modified Eagle's medium. The activity and mRNA expression of CuZn superoxide dismutase (CuZnSOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX) were measured before and after 6 months of treatment with irbesartan (150 mg/day); on both occasions, antioxidant enzyme activity was evaluated at different glucose concentrations (5 and 22 mmol/l). RESULTS: At a normal glucose concentration (5 mmol/l), the activity and mRNA expression of CuZnSOD (0.50 +/- 0.21 units/mg protein, 4.4 +/- 1.5 mRNA/glyceraldehyde-3-phosphate dehydrogenase), MnSOD (0.26 +/- 0.04 units/mg protein, 0.08 +/- 0.07 mRNA), CAT (0.32 +/- 0.08 units/mg protein, 4.8 +/- 1.3 mRNA), and GPX (0.53 +/- 0.09 units/mg protein, 2.2 +/- 0.9 mRNA) were not different among the three groups (only values of diabetic subjects with angiopathy are shown). At high glucose concentrations, the activity and mRNA expression of CuZnSOD increased similarly in all groups (diabetic subjects with angiopathy: 0.93 +/- 0.26 units/mg protein, 9.4 +/- 2.1 mRNA); that of CAT and GPX increased in only control subjects and diabetic subjects without angiopathy (diabetic subjects with angiopathy: 0.33 +/- 0.09 units/mg protein and 5.0 +/- 1.4 mRNA; 0.54 +/- 0.10 units/mg protein and 2.3 +/- 1.0 mRNA, respectively). MnSOD did not change in any group. Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations. Markers of oxidative stress (serum malondialdehyde, fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1, and 8-isoprostanes prostaglandin F(2alpha)) were significantly reduced after treatment with irbesartan. CONCLUSIONS: Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts.
Diabetic retinopathy (DR) remains a major cause of new cases of blindness onset in adults. The prevalence of diabetic eye disease is strongly related to the duration of diabetes, blood pressure and glycemic control, although a multifactorial pathogenesis is likely to be probable. Despite the effectiveness of current prevention (by tight metabolic and blood pressure control) and treatment (with laser photocoagulation) methods, and with the help of screening programs, diabetic eye disease is still a problem. Recent advances in our understanding of the pathogenesis of microvascular complications and particularly of the role of growth factors (GFs) in retinal changes have allowed significant advances in the medical management of DR. Studies of the biochemical process underlying DR have clearly demonstrated an important role for a number of aberrantly expressed GFs or their second messengers (eg, vascular endothelial growth factor, growth hormone, insulin-like growth factor-1, protein kinase C and pigment epithelium derived factor) possibly acting together in the development of structural changes characterizing early stages of vascular DR. The critical role of GF expression has led to new experimental therapeutic intervention in DR. In fact, timely pharmacological intervention in GF synthesis and activities may arrest the development of early vascular changes. As the effects of GFs become better understood, pharmacological manipulation of GF synthesis and action will be useful in the early stages of vascular change with the potential to prevent diabetes-related visual loss.
Treatment for acute lymphoblastic leukaemia can induce alterations of glucose metabolism, but long-term follow-up data on this topic are still absent. We aimed to study glucose metabolism by intravenous and oral glucose tolerance testing in 32 children affected by acute lymphoblastic leukaemia and who were off-therapy for at least 1 year. 22 (69%) children presented with impaired first-phase insulin response, which in nine children was associated with impaired glucose tolerance and in one child with overt diabetes. Fasting insulin (4.65 mU/L, 95% CI 1.1-8.1; p=0.008), insulinogenic index (0.46; 0.02-0.98; p=0.03), and homoeostatic model assessment beta-cell function (80.1, 7.2-153; p=0.02) were reduced in the children with impaired insulin response. Chemotherapy for acute lymphoblastic leukaemia is associated with beta-cell function damage, which persists even after therapy has been stopped.
Type 1 diabetes mellitus (T1DM) and other chronic diseases in children are well known to adversely affect linear growth and pubertal development. In the years immediately following the introduction of insulin therapy, short stature was consistently reported in children with T1DM. However, over the past 50 years significant improvement in the prognosis for growth and final height in children with diabetes has been achieved. Although pre-pubertal and post-pubertal growth are important phases in growth, puberty and its related hormonal changes represent a critical phase for growth gain and final height particularly in patients with T1DM. Growth impairment reported in diabetic patients is dependent on abnormalities in physiological bone growth and corresponds to abnormalities of the growth hormone-insulin-like growth-I (GH-IGF-I) axis. These alterations seem to be related to appropriate insulin levels and thereby to glycaemic control as judged by haemoglobin levels. Modern diabetes care, particularly intensified insulin regimens, might improve metabolic control in patients with T1DM, therefore preventing abnormalities of the GH-IGF-I axis and leading to normal growth and final height similar to that of their unaffected peers.
We report on a male patient with an inactive pituitary and lumbar astrocytoma. He presented with panhypopituitarism at the age of 16 and received growth hormone replacement therapy for one year. During this period the pituitary mass increased substantially and showed subsequently a consistent shrinkage once treatment was stopped. The lumbar lesion stayed stable for the whole period of observation. The presumable rGH related change of the pituitary astrocytoma underlines the importance of careful follow-up of children with growth hormone deficiency secondary to treatment for brain tumors. Substitution therapy with rGH requires further and longer studies before it can be recommended with absolute reassurance in children with subtotal resection of a pituitary astrocytoma.
Nephropathy is the main cause of morbidity and mortality in patients with type 1 diabetes and, in adults, persistent microalbuminuria is the best marker of the consequent risk for its development. In the pediatric population, puberty represents the most important risk factor for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. As many as 50% of subjects may revert to normoalbuminuria. Hypertension is a further risk factor and may accelerate the progression of micro- and macrovascular complications. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects--hence they represent the drug of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific, they may become the obvious treatment choice in the near future. There is no consensus as to who should be treated and when treatment with renoprotective drugs should begin in the pediatric population, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review some models and controversial aspects of this issue are presented and discussed.
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Endothelial dysfunction is defined as the loss of endothelium properties, e.g. alteration of protein synthesis, increased vascular tone and permeability, acquisition of prothrombotic and antifibrinolytic properties. Endothelium, a primary target of unbalanced glycaemic control, is involved in the pathogenesis of vascular complications in patients with type 1 diabetes mellitus (DM). Vascular endothelium damage is characterised by an increase of endothelium-derived regulatory proteins. vWF and t-PA may be useful to investigate early endothelium involvement. However, impaired endothelium-dependent vasodilatation may be a more sensitive marker. Abnormal markers of endothelial cell activation and impaired endothelium-dependent vasodilatation have been observed in young patients with type I DM. Hyperglycaemia may alter normal endothelium functions, either directly or indirectly, by inducing different metabolic pathways. Complete understanding of the pathophysiology of endothelial dysfunction may lead to timely therapeutic intervention to prevent its development and to slow the progression of diabetic complications.
OBJECTIVES: To investigate the possible role of hyperglycemia-dependent monocyte chemoattractant protein (MCP)-1 biosynthesis in the pathophysiology of early nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared with matched healthy control subjects. Plasma MCP-1 and plasma oxidant status (vitamin E, fluorescent products of lipid peroxidation [FPLPs], malondialdehyde [MDA]), HbA(1c), and albumin excretion rate [AER]) were evaluated at baseline. Furthermore, MCP-1, vitamin E, AER, and HbA(1c) were also analyzed in the microalbuminuric diabetic patients and in the healthy volunteers after 8 weeks of high-dose (600 mg b.i.d.) vitamin E treatment. RESULTS: FPLPs, MDA, and MCP-1 were significantly higher, whereas vitamin E was significantly lower in patients with microalbuminuria and poorer glycemic control as compared with normoalbuminuric patients and healthy control subjects. Plasma MCP-1 was positively correlated with HbA(1c), FPLPs, MDA, and AER, whereas plasma MCP-1 showed an inverse correlation with vitamin E. Interestingly, both MCP-1 and AER decreased significantly after vitamin E treatment, despite no changes in HbA(1c) values. CONCLUSIONS: This study suggests that prolonged hyperglycemia may lead to early renal complications in type 1 diabetes by inducing MCP-1 biosynthesis via enhanced oxidative stress. Long-term treatment of high-dose vitamin E significantly decreased MCP-1, thus providing a rationale basis for evaluating vitamin E supplementation as therapy adjuvant to conventional insulin treatment in type 1 diabetic patients in whom an acceptable glycemic control is difficult to achieve despite appropriate insulin treatment.
The following study compares body awareness and body satisfaction of physically handicapped and normal adolescents. In addition the correlations between self image were investigated in the group of handicapped adolescents. The comparison showed handicapped youths to have more negative body image. The handycap-associated differences between the 2 groups were paralleled by equally significant gender-associated differences within the group of handicapped adolescents. The differences are similiar to ones described in the literature as typical for normal adolescents. No evidence was found of minimizing or disavowing the illness or of shame for the handicapped body. Instead, a strong wish for contact with healthy youths was evident. The results of the study underline the importance of body-associated psychotherapeutic intervention supplementing the many therapeutic measures of handicapped adolescence.