Sex-related association of serum uric acid with inflammation, kidney function and blood pressure in type 1 diabetic patients.

BACKGROUND/OBJECTIVE: Recent studies suggest that uric acid (UA) is a mediator of diabetic nephropathy. We hypothesized that serum UA would associate with the prevalence of diabetic nephropathy in youth with type 1 diabetes (T1D), and that this relationship would differ by sex. METHODS: We examined 120 young boys and the same number of girls with T1D. C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor α (TNF-α), UA, cystatin C serum concentrations, albumin excretion rate and blood pressure were also analyzed. RESULTS: T1D boys had higher serum UA and creatinine concentration, as well as albumin excretion rate and estimated glomerular filtration rate than T1D girls. Moreover, newly diagnosed nephropathy was more common in male subjects in comparison to female patients. Only in T1D boys serum UA was positively correlated with concentrations of subclinical inflammatory markers (CRP, IL-6, TNF-α), the indicators of renal function (albumin excretion rate, serum cystatin C level), blood pressure and negatively correlated with anti-inflammatory IL-10. In addition, only in T1D girls serum UA concentration was negatively correlated with hemoglobin A1c. CONCLUSIONS: Serum UA is associated with nephropathy prevalence, albeit only in boys with T1D and may be an important risk factor for predicting diabetes-related cardiorenal complications in these patients.

When do paediatric patients with familial hypercholesterolemia need statin therapy?

INTRODUCTION: Familial hypercholesterolemia (FH) is one of the most common autosomal dominant disorders. It is characterized by elevated LDL cholesterol levels occurring already by early childhood. Awareness of health risks in FH patients should incite health professionals to actively seek and treat children with lipid disorders to reduce their risk of myocardial infarction and stroke. OBJECTIVE: The aim of the study was to evaluate the suitability of taking into account the following parameters: ApoB/ApoA index, IMT and e-tracking examination, when initiating statin therapy in FH patients. Materials and methods The study included 57 male and female patients aged 9.57±3.2 years (ranging from 1 year to 17 years), diagnosed with familial hypercholesterolemia confirmed by molecular testing. All the participants had their lipid profile, ApoA and ApoB levels determined. Carotid intima-media thickness (IMT) was measured by carotid ultrasound and arterial stiffness was assessed by e-tracking. The dietary treatment efficacy was monitored in 40 patients and the 12-month combination treatment efficacy in 27 patients. The study was conducted prospectively and retrospectively. Statistical analysis was performed with the EPIINFO Ver. 7.1.1.14 statistical software package. RESULTS: Patients with familial hypercholesterolemia had high mean levels of total cholesterol and LDL cholesterol (287±67 mg/dL and 213±73 mg/dL respectively). 34.37% of the study subjects had a markedly increased ApoB/ApoA index. On IMT or e-tracking examination all the subjects (100%) had vascular abnormalities. After 6 months of a low-cholesterol diet, the mean total and LDL cholesterol levels in the serum had been reduced by 7.2% and 6.2%, respectively. Statins in an average dose of 10.42±2.49 mg daily were prescribed to 36 patients. After one year of the statin therapy, the average serum total and LDL cholesterol levels were 203.5±34.8 mg/dL and 139.1±32.1 mg/dL, respectively, and were still above the target values. Moreover, side effects of the statin therapy were monitored. An increase in AST levels seen in the study group was not statistically significant. The mean creatine kinase level was within the range of normal. Moreover, in our study material we estimated the risk of cardiovascular events in relation to the ApoB/ApoA index. Higher cardiovascular risk was found in 34.37% participants. CONCLUSIONS: Increased risk of cardiovascular events based on ApoB/ApoA index and carotid e-tracking or IMT examination in paediatric patients with FH is an indication for statin therapy initiation.

CCR5-Δ32 gene polymorphism is related to celiac disease and autoimmune thyroiditis coincidence in patients with type 1 diabetes.

AIM: The aim of the study was to assess the relationship between CCR5-Δ32 polymorphism and the coincidence of celiac and autoimmune thyroid diseases with type 1 diabetes mellitus (T1D) in children. METHODS: 420 children with T1D aged 15.5±3.0years and 350 healthy controls were studied. Characterization of CCR5-Δ32 genotypes (rs333) was analyzed by polymerase chain reaction (PCR). RESULTS: The allele frequency was significantly different in diabetic children as compared to the healthy controls (p<0.0001). We found negative association between T1D and Δ32 allele (OR=0.383; 95% CI=0.268-0.549). Besides, we observed alterations in the frequencies of CCR5-Δ32 genotypes due to celiac and autoimmune thyroid diseases. The risk of celiac disease for patient carriers of the 32-bp deletion was more than threefold higher than for noncarriers (OR=3.490; 95% CI=1.357-8.859; p=0.009). Similar results were obtained in the case of autoimmune thyroiditis. The risk of autoimmune thyroiditis for patient carriers of the 32-bp deletion was also more than threefold higher than for noncarriers (OR=3.466; 95% CI=1.754-6.849; p=0.0004). CONCLUSIONS: The findings of our studies suggest that the CCR5-Δ32 polymorphism is associated with type 1 diabetes mellitus and the Δ32 allele increases the risk of celiac disease and autoimmune thyroid disorders in patients with T1D.

Congenital hyperinsulinism in Polish patients--how can we optimize clinical management?

INTRODUCTION: Congenital hyperinsulinism of Infancy (CHI) comprises heterogenic defects of insulin secretion with diverse molecular aetiology, histological features, severity of symptoms, and response to pharmacotherapy. The study aimed to establish the first clinical characteristics of Polish patients with CHI and to propose a novel clinical algorithm allowing the prioritisation of genetic and radiology studies, based on patient's characteristics and response to pharmacotherapy. MATERIAL AND METHODS: Thirty-one patients with CHI were recruited from five reference centres in Poland. Clinical and biochemical parameters were statistically evaluated and compared to those of a control group (n = 30). RESULTS: CHI predisposes to increased birth weight (p = 0.004), lower Apgar score (p = 0.004), perinatal complications (74%), and neurological implications (48%). Diagnostic process and therapy were inconsistent. A trial of pharmacotherapy was applied in 21 patients (68%), and diagnostic imaging with 18F-L-DOPA PET was performed in only 3. Eighteen patients (58%) were surgically treated, including 8 infants (44%) aged less than 2 months. Depending on the type of resection, further hypoglycaemia was observed postoperatively in 50% (n = 9) and hyperglycaemia in 39% (n = 7) of cases. Based on foregoing results, a clinical algorithm was proposed. CONCLUSIONS: Standardisation of clinical management with the use of pharmacotherapy, genetic screening, and diagnostic imaging will allow the optimisation of therapy and minimisation of treatment complications.

Grade of inflammation in boys with type 1 diabetes depends on the IVS1 -397T>C estrogen receptor α polymorphism.

BACKGROUND AND AIMS: The effect of estrogens is mediated by activation of estrogen receptors (ERs), which are expressed in many tissues. Because ER-α gene polymorphisms may exert different effects in childhood, in the present study we analyzed associations between the IVS1 -397T>C polymorphism and indicators of inflammatory response as well as late complications in boys with type 1 diabetes mellitus (DM1). METHODS AND RESULTS: We examined 108 young boys with DM1 and 64 healthy age-matched control individuals. ER-α genotyping, as well as the CRP and IL-6 serum level and blood pressure, was analyzed. In our study boys with CC genotype had lower blood pressure and IL-6 and CRP serum levels. Similar results were obtained for DM1 boys with microvascular complications - the blood pressure and serum level of IL-6, but not CRP, were still lower in the CC patients. CONCLUSIONS: Our findings suggest that the presence of -397T allele may indicate macro- and microvascular complications in DM1 boys, before the occurrence of first clinical symptoms.

Management of familial hypercholesterolemia in children and adolescents. Position paper of the Polish Lipid Expert Forum.

Familial hypercholesterolemia (FH) affects on average 1 in 500 individuals in European countries, and it is estimated that FH in Poland may affect more than 80,000 people. However, in Poland, only about 20% of the population is estimated to have been diagnosed with FH, of which only a small number receive adequate treatment. FH results in more rapid development of atherosclerosis and is associated with a high risk of cardiovascular events. Atherosclerosis develops beginning in childhood in patients with FH and reaches advanced stages before clinical manifestations develop. Inadequate diagnostics and treatment of FH in Polish children suggests a need for raising the level of awareness and understanding of the condition in both society and among health professionals. These recommendations present the current epidemiological status, guidelines for diagnosing FH in Polish children and adolescents, and effective treatment options.

IVS1 -397T>C estrogen receptor α polymorphism is associated with low-grade systemic inflammatory response in type 1 diabetic girls.

PURPOSE: The study aimed to investigate the influence of estrogen receptor α (ER-α) genotypes on inflammatory response and development of microvascular complications in girls with type 1 diabetes. METHODS: 152 young regularly menstruating girls with diagnosed type 1 diabetes and 84 young, healthy menstruating girls were recruited. ER-α genotyping was carried out by PCR. Serum concentrations of 17ß-estradiol, as well as IL-6, TNF-α, VEGF, and IL-10, were measured. CD4(+)Foxp3(+) TH17 cells were isolated and analyzed by flow cytometry. RESULTS: Type 1 diabetic girls carrying TT genotype were characterized by the lowest serum estradiol level and IL-10 and highest IL-6, TNF-α, and VEGF. The association between the level of certain cytokine and the genetic variant of estrogen receptor α polymorphism was analyzed. Frequencies of CD4(+)Foxp3(+) TH17 cells were also enhanced in TT bearing girls with type 1 diabetes and correlated with the level of analyzed cytokines. In addition, the correlation between serum estradiol level and cytokine concentrations was observed. CONCLUSIONS: We propose that TT variant of estrogen receptor α polymorphism may be associated with enhanced inflammatory response, which in turn may lead to acceleration of diabetic retino- and nephropathy in girls with type 1 diabetes. This finding may help the physicians to predict the onset and progression of diabetic microvascular complications.

The association of the IVS1-397T>C estrogen receptor α polymorphism with the regulatory conditions in longstanding type 1 diabetic girls.

Type 1 diabetes is considered as pluricausal disease, whose etiology involves genetic predisposition as well as environmental factors that contribute to disease progression and pathogenesis. Women are believed to be more susceptible to develop autoimmune diseases, which may depend in part on the influence of sex hormones on the immune system. It was shown that estrogens may protect against the development of autoimmune disease by inducing the expansion of regulatory T cell pool and upregulating Foxp3 expression. Foxp3 is a transcription factor that controls the development and suppressive function of naturally occurring regulatory T cells CD4(+)Foxp3(+). Longstanding diabetes type 1 has features of low-grade chronic inflammation which may influence regulatory T cell subset by reducing their numbers or/and inhibiting their suppressive potential. As diabetic type 1 patients are differentiated with regard to metabolic factors, level of glycemic control and systemic inflammatory state, we aimed to examine if this can be associated with IVSI-397T>C estrogen receptor α polymorphism. We examined 93 young regularly menstruating girls with diagnosed type 1 diabetes and 49 healthy age-matched control individuals. The PvuII polymorphism of the ER-α gene was analyzed as well as the serum TNF level and the level of CD4(+)Foxp3(+) regulatory T cells in these individuals. Girls with type 1 diabetes had lower level of CD4(+)Foxp3(+) Tregs than their healthy counterparts. Regulatory T cells from these patients showed also lower expression of Foxp3 than Tregs in healthy, control group. In addition, DM1 girls bearing the CC genotypes showed the highest level of CD4(+)Foxp3(+) Tregs and the lowest TNF serum level in comparison to girls carrying CT or TT genotype. The CC DM1 carriers had also higher serum level of estrogens than girls bearing CT or TT genotype. We propose that different variants of IVS1-397 estrogen receptor α polymorphism may become additional genetic factor that influences regulatory conditions during diabetes type 1 in females.