Non-invasive detection of early microvascular changes in juveniles with type 1 diabetes.

AIMS/HYPOTHESIS: The study aimed to assess the usefulness of capillaroscopy and photoplethysmography in the search for early vascular anomalies in children with type 1 diabetes. METHODS: One hundred sixty children and adolescents aged 6-18, 125 patients with type 1 diabetes, and 35 healthy volunteers were enrolled in the study. We performed a detailed clinical evaluation, anthropometric measurements, nailfold capillaroscopy, and photoplethysmography. RESULTS: Patients with diabetes had more often abnormal morphology in capillaroscopy (68.60%, p = 0.019), enlarged capillaries (32.6%, p = 0.006), and more often more over five meandering capillaries (20.90%, p = 0.026) compared to healthy controls. Meandering capillaries correlated with higher parameters of nutritional status. In a photoplethysmography, patients with diagnosed neuropathy had a higher percentage of flow disturbance curves (p < 0.001) with a reduced frequency of normal curves (p = 0.050). CONCLUSIONS: Capillaroscopic and photoplethysmographic examinations are non-invasive, painless, fast, and inexpensive. They are devoid of side effects, and there are no limitations in the frequency of their use and repetition. The usefulness of capillaroscopy and photoplethysmography in the study of microcirculation in diabetic patients indicates the vast application possibilities of these methods in clinical practice.

Historical and cultural aspects of obesity: From a symbol of wealth and prosperity to the epidemic of the 21st century.

World Health Organization defines obesity as abnormal or excess adipose tissue accumulation. Nowadays, this condition is a serious threat to the public health in most countries around the world. Obesity adversely affects physical, mental, and in most cultures, social well-being. However, throughout the ages-from ancient times to the 21st century-this condition has been subject to various interpretations. As a matter of fact, obesity has not always been regarded as a disease. For many decades, excessive body weight has been considered rather a symbol of health. It was a marker of wealth and prosperity, as well as a sign of high social status. The centuries that passed on the development of science and medicine have gradually changed its face, but significant progress in understanding the causes and consequences of obesity has been made in the last 30 years. This paper presents the historical outline of obesity and its treatment from ancient times to the present-from its affirmation to the epidemic in the late 20th and 21st century.

Non-Classic Disorder of Adrenal Steroidogenesis and Clinical Dilemmas in 21-Hydroxylase Deficiency Combined with Backdoor Androgen Pathway. Mini-Review and Case Report.

Congenital adrenal hyperplasia (CAH) is the most common cause of primary adrenal insufficiency in children and adolescents. It comprises several clinical entities associated with mutations in genes, encoding enzymes involved in cortisol biosynthesis. The mutations lead to considerable (non-classic form) to almost complete (classic form) inhibition of enzymatic activity, reflected by different phenotypes and relevant biochemical alterations. Up to 95% cases of CAH are due to mutations in CYP21A2 gene and subsequent 21α-hydroxylase deficiency, characterized by impaired cortisol synthesis and adrenal androgen excess. In the past two decades an alternative ("backdoor") pathway of androgens' synthesis in which 5α-androstanediol, a precursor of the 5α-dihydrotestosterone, is produced from 17α-hydroxyprogesterone, with intermediate products 3α,5α-17OHP and androsterone, in the sequence and with roundabout of testosterone as an intermediate, was reported in some studies. This pathway is not always considered in the clinical assessment of patients with hyperandrogenism. The article describes the case of a 17-year-old female patient with menstrual disorders and androgenization (persistent acne, advanced hirsutism). Her serum dehydroepiandrosterone sulfate and testosterone were only slightly elevated, along with particularly high values for 5α-dihydrotestosterone. In 24 h urine collection, an increased excretion of 16α-OHDHEA-a dehydroepiandrosterone metabolite-and pregnanetriolone-a 17α-hydroxyprogesterone metabolite-were observed. The investigations that we undertook provided evidence that the girl suffered from non-classic 21α-hydroxylase deficiency with consequent enhancement of the androgen "backdoor" pathway in adrenals, peripheral tissues or both, using adrenal origin precursors. The paper presents diagnostic dilemmas and strategies to differentiate between various reasons for female hyperandrogenism, especially in childhood and adolescence.

STAT4 sequence variant and elevated gene expression are associated with type 1 diabetes in Polish children.

INTRODUCTION: Type 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic ß cells, resulting from coincident genetic predisposition and some environmental triggers. Signal transducer and activator of transcription 4 (STAT4) gene encodes a transcription factor, which promotes Th1 cell differentiation, interferon γ production, and development of Th17 cells. Polymorphisms of STAT4 are associated with several autoimmune conditions, while studies in T1D provided inconsistent results. This analysis was designed to investigate the association of STAT4 rs7574865 with T1D in Polish children and to assess STAT4 expression in newly diagnosed subjects. MATERIAL AND METHODS: Rs7574865 was genotyped in 656 T1D children and 782 healthy individuals. STAT4 mRNA expression was analyzed in peripheral blood mononuclear cells (PBMCs) from 29 children with T1D and 27 age-matched controls. ß-cell and thyroid-specific serum autoantibodies were assessed with radioimmunoassays. RESULTS: The distribution of rs7574865 genotypes and alleles demonstrated significant difference (p = 0.002, p < 0.001, respectively) between patients vs. controls. Carriers of the minor T allele presented earlier T1D onset (p = 0.017). No differences were found in γ-cell autoantibody in genotype-stratified patients (p > 0.050), while anti-thyroid antibodies were more frequent in carriers of the minor allele(p = 0.039 for anti-thyroperoxidase, p = 0.007 for anti-thyroglobulin antibodies, respectively). STAT4 was overexpressed in PBMCs from T1D patients (p = 0.008), especially subjects with two/three circulating ß-cell antibodies (p < 0.001). CONCLUSIONS: The study confirms an association of STAT4 rs7574865 with T1D in Polish patients, and provides an evidence for its relationship with an earlier disease onset and concomitant thyroid autoimmunity. STAT4 expression appears elevated in T1D, especially with more severe reaction against ß-cell antigens.