Next- generation sequencing is an effective method for diagnosing patients with different forms of monogenic diabetes.

AIM: Monogenic diabetes (MD) represents 5-7% of antibody-negative diabetes cases and is a heterogeneous group of disorders. METHODS: We used targeted next-generation sequencing (NGS) on Illumina NextSeq 550 platform involving the SureSelect assay to perform genetic and clinical characteristics of a study group of 684 individuals, including 542 patients referred from 12 Polish Diabetes Centers with suspected MD diagnosed between December 2016 and December 2019 and their 142 family members (FM). RESULTS: In 198 probands (36.5%) and 66 FM (46.5%) heterozygous causative variants were confirmed in 11 different MD-related genes, including 31 novel mutations, with the highest number in the GCK gene (206/264), 22/264 in the HNF1A gene and 8/264 in the KCNJ11 gene. Of the 183 probands with MODY1-5 diabetes, 48.6% of them were diagnosed at the pre-diabetes stage and most of them (68.7%) were on diet only at the time of genetic diagnosis, while 31.3% were additionally treated with oral hypoglycaemic drugs and/or insulin. CONCLUSIONS: In summary, the results obtained confirm the efficacy of targeted NGS method in the molecular diagnosis of patients with suspected MD and broaden the spectrum of new causal variants, while updating our knowledge of the clinical features of patients defined as having MD.

Growth Hormone Treatment Increases Plasma Irisin Concentration in Patients with Turner Syndrome.

Irisin (Ir) deficiency may be a contributing factor in metabolic disease. This study aimed to investigate the effect of supraphysiological doses of recombinant human growth hormone (rhGH) on Ir plasma concentration in relation to metabolic disorders, including obesity and other components of metabolic syndrome. We studied 36 girls with Turner syndrome (mean age 8.2 years) treated with rhGH (0.05 mg/kg/day). Anthropometric data and fasting blood levels [e. g., Ir, insulin, glucose, glycated hemoglobin (HbA1c), IGF-1, IGFBP-3, cholesterol, insulin resistance (HOMA-IR), and ß-cell function (HOMA-ß)] were analyzed prior to and following rhGH therapy [mean (SD) follow-up of 1.47 (0.89) years]. Insulin sensitivity (Matsuda index) was calculated before and after the glucose load. Following rhGH therapy, an increase in IGF-1 [mean (SD) of 119.40 (62.47) ng/ml to 439.08 (209.91) ng/ml, p=0.000], Ir [2.10 (1.03) µg/ml to 2.48 (0.78) µg/ml, p=0.036], HOMA-IR [median (IQR) of 0.64 (0.45-1.30) to 0.92 (0.67-2.36), p=0.0206], and HOMA-ß values [45.00 (27.69-72.00) to 81.53 (51.43-132.00), p=0.0447] were observed. Multiple regression analysis yielded no associations between Ir and metabolic and hormonal parameters before rhGH treatment; however, on rhGH, the model (R2=0.56, adjusted R2=0.45) showed positive associations between Ir and IGF-1 standard deviation score and HbA1c, and negative associations between Ir and fasting blood glucose, HDL-cholesterol, and triglycerides. Despite manifestation of insulin resistance, rhGH application had a positive effect on Ir regulation, and restored physiological conditions of lipid and glucose metabolism.

A novel p.E311K mutation of thyroid receptor beta gene in resistance to thyroid hormone syndrome, inherited in autosomal recessive trait.

Resistance to thyroid hormone (RTH) syndrome is caused by mutations in THRB gene and is inherited mainly as an autosomal dominant trait with dominant negative effect. Most of up-to-now described RTH cases were heterozygous. We studied a 19-year-old woman presenting severe mental impairment, hyperkinetic behavior, learning disability, hearing loss, tachycardia, goiter, strabismus, nystagmus, and normal stature. The laboratory findings revealed elevated TSH, T3, and T4 serum levels. Her parents were healthy with normal serum level of TSH, fT3, and fT4. Sequence based prediction of a substitution was analyzed by SDM, PolPhen, and SNAP software whereas structural visualizations were performed in UCSF Chimera. We found a novel mutation in THRB gene in position 1216 (G to A transition, codon 311) resulting in novel Glu-311-Lys (p.E311K) substitution, homozygous in proband presenting with severe symptoms of RTH and heterozygous in both of her healthy parents, thus suggesting autosomal recessive mode of inheritance. p.E311K substitution was not found in 50 healthy, unrelated individuals. p.E311K was shown to be deleterious by SDM, PolPhen, and SNAP software. Structural visualizations of mutated protein performed by UCSF Chimera software disclosed a loss of hydrogen bonds between E311, R383, and R429 along with abnormal residue-residue contact between K311 and L377. This is a very rare case of a homozygous mutation in a patient with severe symptoms of RTH and lack of symptoms in both heterozygous parents. Although, computational analyses have provided the evidence that p.E311K substitution may affect THRB function, lack of dominant negative effect typical for THRB mutations could not be explained by structure-based modeling. Further in vitro analysis is required to assess the functional consequences of this substitution.

Sudden hearing loss as a first complication of long-standing Type 1 diabetes mellitus: a case report.

The term 'sudden hypoacusis' describes a hearing loss of a rapid onset and unknown origin that can progress to severe deafness. Its pathophysiology is still unknown, the proposed aetiological mechanisms being vascular disease or autoimmune reaction. We present the case of a 19-year-old woman with Type 1 diabetes mellitus who experienced sudden hearing loss on her right side. She had no complications related to diabetes. After being referred to the hospital she was diagnosed with sudden sensorineural right-sided hearing loss accompanied by high frequency tinnitus. After administration of vasoactive drugs, there was partial improvement after 7 days, followed by gradual improvement over the next 4 weeks to 5 months. The tinnitus did not disappear completely. We conclude that hearing organ disturbances can be present in Type 1 diabetes and represent an early complication.

Distribution of Ca.LSU intron and acid protease production by Candida albicans strains isolated from gastrointestinal tract of diabetes children.

The association between the presence of self-splicing intron Ca.LSU and proteolytic activity of Candida albicans isolates was tested. Study included 95 C. albicans strains isolated from gastrointestinal tract of diabetes children. The strains with the intron (genotype B) displayed a significantly higher proteolytic activity (385.2+/-192U/L) than did strains without intron (genotype A) (119+/-115U/L) (p = 0.0000048).

Are there any disturbances in vestibular organ of children and young adults with Type I diabetes?

AIMS/HYPOTHESIS: The aim of the work was to evaluate the vestibular organ condition in children and young adults suffering from Type I (insulin-dependent) diabetes mellitus. METHODS: The group examined consisted of 95 children and young adults aged from 6 to 28 years with Type I diabetes diagnosed. The diabetic group was divided into subgroups according to duration of the disease, compensation of the disease, and presence and character of hypoglycaemic incidents, and presence of diabetic complications. The control group consisted of 44 healthy children and young adults aged 6 to 28 years. After collecting detailed medical history in each case an electronystagmographic test was performed using the computed two-canal electronystagmographer. RESULTS: Within the diabetic group 6 patients complained about vertigo and balance disorders. Spontaneous nystagmus occurred in 10 cases, positional one in 21 cases. Impaired optokinesis occurred in 36 cases and impaired eye tracking test in 33 cases. In caloric tests there was partial canal paresis in 4 cases and directional preponderance in 7 cases. CONCLUSION/INTERPRETATION: Metabolic disturbances present in Type I diabetes cause disturbances in different parts of vestibular organ but mostly in its central part. Comparing disturbances in the vestibular organ with clinical and biochemical parameters characterising diabetes, the range of vestibular organ impairment in diabetes mellitus type 1 seems to depend mainly on the presence and character of hypoglycaemic incidents and the duration of the disease and to some extent on the compensation of diabetes.

[Hypersensitivity of estrogen receptors as a cause of gigantomasty in two girls]. / Nadwrazliwosc receptorów estrogenowych jako powód gigantomastii u dwóch dziewczynek.

The authors present two girls with gigantomastia, 14 and 15 years of age. Laboratory examinations demonstrate an increase of estrogen receptors in the glandular tissue. In the immunohistochemical investigations ascertained was a receptor hypersensitivity of estrogen and progesterone receptors. In one of the girls shown was hyperprolactinemia in the metoclopramide test (patient J.K.) In the physical examination hyperlordosis, kyphosis, gigantomastia was observed. Additional in patient K.S.--anorexia and patient J.K.--Sjögren's syndrome.

[Actual treatment with insulin in children and adolescents with diabetes type 1]. / Wspólczesne metody insulinoterapii cukrzycy typu 1 w wieku rozwojowym.

A significant progress in the therapy of type 1 diabetes has been achieved. This was mainly because glucometers are now introduced in the majority of patients, better pens for insulin injections are now available. A progress was done in the methods of education and insulin analogues like Humalog were introduced. Therefore it is now possible to achieve a better metabolic compensation because of a more physiologic insulin action. A further progress is the introduction of long acting analogues and personal insulin pumps for the therapy. There are a lot of examinations about the epidemiology and prophylaxis of diabetes.

[Phenylketonuria and diabetes type 1 in a 13 year old boy-six years observation]. / Fenyloketonuria i cukrzyca typu 1 u 13-letniego chlopca - szescioletnia obserwacja.

The author presented the development and the results of biochemical, metabolic, genetic and immunological examinations of a boy aged 13 with phenylketonuria, in whom at the age of seven diabetes type 1 was diagnosed. The physical and psychical development was normal after a period of six years and the control examinations of HbA1c and phenylalanine in the Guthrie test were in normal range. The received results testify to a proper treatment of diabetes as well as phenylketonuria in the observed child.

[Dietary guidelines in diabetes mellitus type 1]. / Zalecenia zywieniowe w cukrzycy typu 1.

The diet has basic meanings for treatment of every kinds of diabetes. The proper function of organism and protection against negative causes of malnutrition is the aim of diet. The calorical value of nutrition and vitamins, mineral salts and fibre should not differ from healthy. The diet of a child with diabetes should have bigger caloric values which comes from greater needs of growing organism and additional energetic needs, for example physical exercises.

Goiter prevalence in children in Lower and Middle Silesia (Wroclaw--coordinating center).

As a part of the programme concerning iodine deficiency and iodine prophylaxis in Poland, 2518 children of age between 6 and 13 years, living in Lower and Middle Silesia, were studied. The anamnesis was based on a questionnaire answered by parents of the investigated children. The physical examination included measurements of body height and mass, clinical symptoms of thyroid functions as well as size and compactness of the thyroid gland on the basis of WHO classification. Urinary concentration of iodine was measured. The majority of children with goiter were inhabitants of mountainous villages. The goiter was most frequent in the age group 9-10 years. No significant differences in goiter incidence could be found between children consuming and not consuming iodized kitchen salt. The urinary concentration of iodine was low in all children examined. It was concluded that the territory of Lower and Middle Silesia is still a region of moderate endemic goiter. The urinary iodine concentrations is low in children living in Lower and Middle Silesia. The present system of iodine prophylaxis is not adequate and new measures should be urgently introduced.