Assessment of preservation of beta-cell function in children with long-standing type 1 diabetes with "ultrasensitive c-peptide" method.

INTRODUCTION: Type 1 diabetes mellitus is a disease caused by the autoimmune destruction of pancreatic beta-cells. It was previously believed that the loss of the endocrine function of the pancreas is total and inevitable. With the rise of new knowledge and new methods allowing to reliably measure c-peptide in the low plasma concentration range, we have learned otherwise. Some residual function of the beta-cells can be present even after decades of the course of the disease. The aim of the study was to evaluate the c-peptide level with routine laboratory and ultrasensitive methods in children with long-standing type 1 diabetes in relation to clinical characteristics. METHODS: We recruited 178 consecutive children with type 1 diabetes mellitus lasting at least 1 year, mean diabetes duration was 5.6 years. Basic anthropometric measurements were performed and blood samples were drawn. From patients history records we gathered data regarding the course of the disease and laboratory results previously acquired. Laboratory tests performed on the blood samples included HbA1c levels and c-peptide level measurement using classic (n=178) and ultrasensitive (n=160) method (Mercodia). Clinically relevant c-peptide level was set at 0.23 ng/ml according to the DCCT recommendations. RESULTS: Clinically relevant c-peptide was found in 54 of 160 (33.75%) patients. Patients with preserved c-peptide were older at the time of diagnosis, had longer clinical remission, and required lower total and basal doses of insulin. Significantly lower mean HbA1c from the last year, but higher HbA1c at the time of the diabetes diagnosis were found in the group with higher c-peptide levels. The comparison of the classic and ultrasensitive c-peptide tests revealed that both yield similar results. CONCLUSIONS: Our observation shows that 34% of young patients with long-standing type 1 diabetes have prolonged c-peptide secretion. We confirm the long-standing assumption that residual beta-cell function is beneficial for metabolic control of the patients. Classic method of the c-peptide measurement can be just as useful in clinical practice as the ultrasensitive one.

Significant differences in parameters of glucose metabolism in children of hypertensive and normotensive parents.

INTRODUCTION: In the recent years, alterations in the carbohydrate metabolism, including insulin resistance, are considered as risk factors in the development of hypertension and its complications in young age. Hypertension is associated with significant cardiovascular morbidity and mortality. The onset of pathology responsible for the development of hypertension, as well as levels of biomarkers specific for early stages of atherosclerosis are poorly understood. AIM: To compare a group of children whose parents have a history of hypertension (study group) with a group of children with normotensive parents (reference group), with consideration of typical risk factors for atherosclerosis, parameters of lipid and carbohydrate metabolism, anthropometric data and new biomarkers of early cardiovascular disease (hsCRP, adiponectin, sICAM-1). MATERIAL AND METHODS: The study population consists of 84 children. Of these, 40 children (mean age 13.6±2.7 years) had a parental history of hypertension, and 44 aged 13.1±3.7 yrs were children of normotensive parents. Anthropometric measurements were taken, and measurements of blood pressure, lipid profile, glucose and insulin levels were carried out. The insulin resistance index (HOMA IR) was calculated. Levels of hsCRP, soluble cell adhesion molecules (sICAM) and adiponectin were measured. RESULTS: There were no statistically significant differences in anthropometric parameters (body mass, SDS BMI, skin folds) between groups. Values of systolic blood pressure were statistically significantly higher in the study group (Me 108 vs. 100 mmHg, p= 0.031), as were glycaemia (Me 80 vs. 67 mg/dl p<0.001) and insulinaemia levels (Me 8.89 vs. 5.34 µIU/ml, p=0.024). Higher, statistically significant values of HOMA IR were found in the study group (children of hypertensive parents) (Me 1.68 vs. 0.80 mmol/l × mU/l, p=0.007). Lower adiponectin levels (Me 13959.45 vs. 16822 ng/ml, p=0.020) were found in children with a family history of hypertension. No significant differences were found in the levels of sICAM, hsCRP, and parameters of lipid metabolism. CONCLUSIONS: Family history of hypertension is correlated with higher values of systolic blood pressure and higher values of parameters for carbohydrate metabolism in children. Hypertension in parents is a risk factor for cardiovascular disease in their children.

A follow-up history of young man with apparent cortisone reductase deficiency (ACRD) - several years after diagnosis.

INTRODUCTION: Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH), the enzyme responsible for NADPH generation playing critical role in 11-hydroxysteroid dehydrogenase type 1 (11b-HSD1) activity, cause apparent cortisone reductase deficiency (ACRD). It leads to increased metabolic clearance rate of cortisol due to a defect in cortisone to cortisol conversion by 11b-HSD1. We want to analyse the process of the disease, efficacy of long-lasting treatment with glucocorticoids throughout childhood and adolescence in only male patient with ACRD. CASE PRESENTATION: A 23 year-old male patient was diagnosed with ACRD at the age of 7 years. The clinical manifestation of ACRD was presented by precocious pubarche. His bone age was assessed as 11.5 years old. Blood tests indicated increased the plasma androgen, with elevated 17-hydroxyprogesterone concentration. A steroid profile analysis of a 24-h urine collection showed extremely reduced THF + allo-THF/THE ratio - 0.021 (normal range: 0.7-1.2). Two months of hydrocortisone therapy was ineffective and dexamethasone was administered in initial dose of 0.375 mg/24 h. Next dosage beetwen 0.125 mg/24h and 0.375 mg/24h has been changed depending on the patient's results of laboratory tests and condition. Control laboratory studies indicated suppression of excess adrenal androgen synthesis, but we never got the THF + allo-THF/THE ratio in normal values. He did not develop any serious side effects, although dexamethasone is the most potent adrenal suppression drug. CONCLUSIONS: Hydrocortisone treatment is ineffective in ACRD patients because it was rapidly metabolized to cortisone. We have found the balance between the dexamethasone treatment effects of adrenal suppression and the achievement of full height potential considering the condition of our patient.

[Is soluble thrombomodulin a molecular marker of endothelial cell injury in children and adolescents with arterial hypertension?]. / Czy rozpuszczalna trombomodulina (STM) jest markerem uszkodzenia sródblonka naczyn u dzieci i mlodziezy z nadcisnieniem tetniczym?

INTRODUCTION: Endothelial damage is an early step in the pathogenesis of atherosclerosis which begins in early childhood after exposure to atherogenic risk factors such as arterial hypertension. Atherosclerosis is becoming a common disease even in children and adolescents. Its progression may lead to very severe cardiovascular complications. Thrombomodulin (TM), a specific marker of endothelial cell damage, is a transmembranous glycoprotein with vasoprotective and anti-coagulant properties. TM-thrombin complex becomes an activator of protein C which inactivates factor Va and VIIIa and thereby inhibits the blood coagulation cascade. TM may be cleaved to its soluble (sTM) form by proinflammatory mediators and then detected in the circulation. AIM: The aim of the present study was to investigate if sTM plasma concentration--one of biochemical markers of endothelium injury--is higher in children and adolescents with arterial hypertension (AH). MATERIALS AND METHODS: We studied 32 children with hypertension (9 girls and 23 boys, age range 10.5-17.2 years), and 17 healthy controls, without family history of cardiovascular diseases. Hypertension was detected after 24 hrs ABPM (Ambulatory Blood Pressure Monitoring). We measured plasma concentration of sTM, blood lipids profile, body mass index (BMI) and, as sTM is excreted by the kidney, we also measured plasma level of creatinine and its clearance. RESULTS: Plasma concentration of sTM in the group with essential hypertension was significantly higher than that in the control group (4.01 +/-1.05 vs 3.42+/-0.4; p<0. 05). There were no significant associations between sTM and age or sex. Analyzing lipids profile (cholesterol, LDL-c, HDL-c, triglycerides) we did not find any differences in their levels between groups. We observed statistically significant correlation between sTM and systolic and diastolic blood pressure during the day and night. In addition BMI ratio was higher in AH group but there was no significant correlation between sTM and BMI. CONCLUSION: Statistically higher level of sTM in children with AH compared with healthy individuals makes us sure that endothelium cells, even in children who were shortly exposed to atherogenic risk factors such as essential hypertension, are noticeably damaged. These results constitute an additional signal that a lot of effort should be put into the endeavors to eliminate atherogenic risk factors in children in order to prevent cardiovascular events.

[Soluble thrombomodulin--a molecular marker of endothelial cell injury in children and adolescents with obesity]. / Rozpuszczalna trombomodulina -- marker uszkodzenia sródblonka u dzieci i mlodziezy z otyloscia prosta.

BACKGROUND: Endothelial damage is an early step in the pathogenesis of atherosclerosis which begins in early childhood after exposure to atherogenic risk factors such as obesity. Its progression may lead to very severe cardiovascular complications. TM -- a specific marker of endothelial cell damage, is a transmembranous glycoprotein with anti-coagulant properties. It has a large, extracellular region comprising a thrombin binding site. TM-thrombin complex becomes an activator of protein C which inactivates factor Va and VIIIa and thereby inhibits the blood coagulation cascade. OBJECTIVES: The aim of the present study was to investigate if plasma concentration of sTM (one of markers of endothelial cells injury) is higher in children and adolescents with obesity. MATERIALS AND METHODS: We studied 22 obese children, 11 girls and 11 boys, (age range 8.5-17.8 years), and 17 normal weight healthy controls, (age range 12-17.9 years) without family history of cardiovascular diseases. We measured plasma concentration of sTM, blood lipids profile, body weight and BMI. As sTM is excreted by the kidney we also measured plasma level of creatinine and its clearance. RESULTS: Plasma concentration of sTM in the group with obesity was significantly higher than that in the control group. There were no significant association between sTM and age or sex. Compared with non-obese patients, obese children had higher plasma concentration of total cholesterol, LDL-c, triglycerides, but these were not significant differences. However there was a significantly lower level of HDL-c in children with obesity. In addition statistically significant correlation between sTM and BMI was observed in the obese group. CONCLUSIONS: Statistically higher level of sTM in children with obesity compared with healthy individuals makes us sure that endothelium cells, even in children who were shortly exposed to atherogenic risk factors such as obesity, are noticeably damaged. These results constitute an additional signal that a lot of effort should be put into the endeavors to eliminate atherogenes risk factors in children population in order to prevent cardiovascular events.