The present study aims to investigate islet autoimmunity and susceptibility to type 1 diabetes (T1D) in children/adolescents with autoimmune thyroid disease (AITD, and family members of AITD patients ...with islet autoimmunity. Islet-cell cytoplasmic, glutamic-acid decarboxylase, and tyrosine-phosphatase autoantibodies were measured in 161 AITD patients (127 with autoimmune thyroiditis (AT); 34 with Graves' disease (GD), 20 family members of AITD patients with islet autoimmunity, and 155 age-matched controls. Islet autoimmunity was found in 10.6% of AITD patients, significantly more frequent than in controls (1.9%; p=0.002). A higher prevalence of islet autoantibodies was found in females with AITD (p=0.011) but not in males (p=0.16) and AT (p=0.013) but not in GD patients (p=0.19), compared to corresponding controls. Two or three islet autoantibodies were found concurrently in six AITD patients with islet autoimmunity. They all developed T1D and had significantly higher islet autoantibodies titers (p=0.01) than AITD patients with single islet autoantibodies but normal glucose metabolism. T1D was found in 3.7% of AITD patients compared to 0.2% of the age-matched, general Croatian population. Islet autoantibodies were found in 5/20 family members of AITD patients with islet autoimmunity, among which two developed T1D. None of the controls was positive to more than one islet autoantibody or developed T1D. Conclusion: Children/adolescents with AITD (particularly females and patients with AT) represent a risk group for islet autoimmunity and T1D, as well as family members of AITD patients with positive islet autoantibodies, but the last observation must be examined in a more significant number of patients.
Triple A syndrome, caused by autosomal recessively inherited mutations in the
gene is characterized by alacrima, achalasia, adrenal insufficiency, and neurological impairment. To the best of our ...knowledge, no patients of both sexes have been reported to have offspring. Our aim was to assess the causes of infertility in male patients with this multisystemic syndrome, and to present a female patient that spontaneously conceived a child.
Cross-sectional study.
Six males aged 19-48 years were included. Gonadotropins, testosterone, DHEAS, androstenedione, inhibin B, anti-Mullerian hormone measurements and testicular ultrasound were performed.
All six male patients had impaired general health and neurological symptoms including erectile and ejaculatory dysfunction. None of them had an offspring. The only demonstrated cause of infertility in our male patients was erectile and ejaculatory dysfunction which precludes sexual intercourse. Our patients had normal libido but were sexually abstinent. Except for low adrenal androgen levels, the concentrations of all measured hormones as well as testicular ultrasound were normal which may indicate the possibility of spermatogenesis in male patients with triple A syndrome. Little is known about fertility in female patients, but based on our observations spontaneous pregnancies seem to be possible.
Our results contribute to still scarce knowledge on fertility in patients with Triple A syndrome and as well represents a foundation for further research on causes of infertility and possible treatment options.
Diabetes mellitus (DM) is characterized by high blood glucose; impairment of the skeleton is among its other deleterious effects. Adverse effect upon the bone tissue is primarily altered bone quality ...and consequently increased bone fragility. In DM 1, bone mass may be low and in DM2 normal or even increased. Therapy for DM2 also affects bone metabolism as thiazolidine-diones cause differentiation shift of mesenchyme precursors from osteoblasts into adipocytes. Association of bone with glucose metabolism was discovered in the last decade indicating that insulin is necessary for synthesis of undercarboxylated osteocalcin which acts in a hormonal fashion to promote insulin secretion in the pancreas, adiponectin in adipocytes, and increases
insulin sensitivity in target tissues. Undercarboxylated osteocalcin is
also secreted from resorbed bone. Thus insulin is required for normal bone metabolism and bone acts as an endocrine organ. Additional role of osteocalcin is in promoting testosterone secretion in testes.
Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is a rare autosomal recessive disorder caused by pathological variants in the
gene. After a high prevalence of classic ...21-OHD CAH in the Romani population was reported in the Republic of North Macedonia, we decided to estimate the prevalence of 21-OHD in Croatia and, if high, assess the possible causes and estimate the frequency of particular
variants.
Cross-sectional study.
Data from a Croatian 21-OHD genetic database was reviewed, and only Romani patients were included in the study.
genotyping was performed using allele-specific PCR, MLPA, and Sanger sequencing.
According to a survey conducted in 2017, Croatia had 22,500 Romani people and six of them had a salt-wasting (SW) form of 21-OHD. All were homozygous for the c.IVS2-13A/C-G pathological variant in intron 2 and descended from consanguineous families belonging to different Romani tribes. The calculated prevalence of 21-OHD in Croatian Romani is 1:3,750, while in the Croatian general population, it is 1:18,000. Three of the six Romani patients originated from two neighboring villages in North-western Croatia (Slavonia County), as well as the seventh patient who is of mixed Romani/Croatian descent and heterozygous for the c.IVS2-13A/C-G pathological variant (not included in the prevalence calculation).
A high prevalence of SW 21-OHD in the Croatian Romani population caused by the homozygous cIVS2-13A/C-G pathological variant was found. In addition to isolation and consanguinity, other possible reasons could be the heterozygous advantage of the
gene pathological variant and the bottleneck effect as a result of the Romani Holocaust in World War II.
Introduction
Glucagon-like peptide-1 (GLP-1) has many effects on the human body, but its glucose-lowering effect through its stimulation of insulin secretion is the most significant. GLP-1 also acts ...on renal function and hemodynamics. The antihypertensive and renoprotective effects of GLP-1 receptor agonists are partly explained by their vasoactive effect and increased natriuresis, but their positive influences on blood pressure and the development and progression of kidney disease are attributed to many effects beyond glycemic control. The aim of this study was to determine how the native gut hormone GLP-1 influences the renin–angiotensin–aldosterone system (RAAS).
Methods
Fourteen healthy participants (6 males and 8 females) were included in a double-blind, placebo-controlled crossover study. After overnight fasting and oral sodium loading, participants were randomly assigned to receive either placebo (500 ml of 0.9% saline) or GLP-1 infusion (1.5 pmol/kg/min dissolved in 500 ml of 0.9% saline) over a 3-h period. After 3 and 6 h, the following parameters were measured: glucose, insulin, plasma renin activity, aldosterone, GLP-1, and antidiuretic hormone. After 7 days, the protocol was repeated, except that those who had previously received placebo now received GLP-1 infusion, and those who had previously received GLP-1 now received placebo.
Results
Three hours after GLP-1 infusion, aldosterone had decreased by a statistically significant amount (
p
< 0.008) compared to the baseline level.
Conclusion
The present study showed that native GLP-1 can decrease aldosterone secretion in a group of healthy individuals, supporting the idea of beneficial outcomes of GLP-1-activating agents on blood pressure and the RAAS.
Trial Registration
ClinicalTrials.gov Identifier: NCT02130778.
Background High goiter prevalence caused by iodine deficiency (medium content 5.6 mg potassium iodide KI/kg of salt, median urine iodine concentration UIC 68 μg/L) in Croatia was observed in 1991 and ...1995 when salt was iodized with 10 mg KI/kg. A new regulation introduced in 1996, specified 25 mg KI/kg of salt resulting in an increase of median UIC to 248 μg/L. Afterwards, goiter prevalence was only assessed in two small studies. Methods In this study, we investigated the prevalence and etiology of goiter in 3594 schoolchildren 17 years after an increase in salt iodization in Croatia. Thyroid size was determined by palpation in 1777 girls and 1817 boys aged 10-18 years. In goitrous children, a thyroid ultrasound and thyroid-stimulating hormone, free thyroxine (fT4), free triiodothyronine (fT3), thyroid peroxidase (TPO) and thyroglobulin (TG) antibody measurements were performed. Results Goiter was found in 32 children (0.89% vs. 2.8% in 1991, p<0.00001 and 27% in 1995, p<0.00001), simple goiter (SG) in 18/32 (56%) goitrous children vs. 126/152 (82.8%) in 1991 p<0.00001, autoimmune thyroiditis (AT) in 13/32 (40.6%) vs. 19/152 (12.5%) in 1991 p<0.0009, nodules in four: two cysts, toxic adenoma and carcinoma (in 1991 two adenomas and one cyst), Graves' disease was not found (four in 1991). Subclinical hypothyroidism was found in three children. Thyroid disease was diagnosed in four of 32 children before the investigation. Increased iodine supply decreased goiter prevalence and SG/AT ratio in goitrous patients. Conclusions As thyroid abnormalities were found in 0.89% of children and some required treatment, thyroid examination is important in apparently healthy children regardless of sufficient iodization.
The beneficial effect of physical activity on the musculoskeletal health in dogs is well recognized, but the level of intensity, duration, and frequency of exercise is not fully described. ...Measurement of serum markers of bone metabolism (bone alkaline phosphatase and osteocalcin as bone formation markers and C-terminal telopeptide as bone resorption marker) during four months of organized moderate-intensity physical training in Labrador retriever and Golden retriever dogs aged between 11.7–24.4 months, showed variations of bone metabolism. Dogs were included in treadmill running sessions for 25 min, three times per week. Blood samples were taken at the beginning of the program (baseline), after two months (mid-term) and at the end of the study after four months. The values of bone alkaline phosphatase and osteocalcin significantly decreased following two months of exercise program. Bone alkaline phosphatase increased by the end of four-month training cycle, but did not reach baseline value. Osteocalcin levels continued to decrease towards the end of the study. C-terminal telopeptide concentrations did not significantly change throughout the study duration. The results of this study show that aerobic exercise of moderate-intensity caused an initial decrease in bone formation followed by an increase of bone alkaline phosphatase and a further decrease of osteocalcin concentration. The response of two formation markers can be explained by the different stage of osteoblast activity that they express. In summary, moderate exercise resulted in no change in bone resorption, and a mild bone formation in young developing dogs.
Gastrointestinal tract is an important connector between food intake and body weight, it senses basic tastes in a similar manner as the tongue. The aim of the study was to find out how gut hormone ...glucagon-like peptide-1 (GLP-1) influences taste preference. Fourteen healthy participants (six male and eight female) were included in this double-blind, placebo-controlled crossover study. After overnight fast and salty fluid (oral sodium load), participants were randomized to receive placebo (500 mL of 0.9% saline) or GLP-1 infusion (1.5 pmol/kg/min) over a 3-hour period. At the end of infusion, participants chose food preferences from illustrations of food types representing 5 tastes. After 7 days, the protocol was repeated, this time those that had received placebo first got GLP-1 infusion, and those having received GLP-1 first got placebo. Change of taste preference after GLP-1 infusion but not after placebo was reported as response, and non-response was reported in case of taste persistence. A statistically significant difference in response type was found between genders, with women being more likely to change their taste preference after GLP-1 than men. The change of taste upon GLP-1 infusion observed in women might be ascribed to estrogen weight-lowering effects accomplished by receptor-mediated delivery.