Importance of diet in children and adolescents with obesity and asthma.

Both obesity and asthma are increasingly being diagnosed in the childhood population. Obesity is linked to a greater asthma morbidity, and it increases the risk of severity of the disease course. The association between these 2 disorders has not yet been fully elucidated; however, several putative factors have been proposed related to mechanical and inflammatory aspects of obesity. Diet is an important adjustable element in obesity and asthma management. An unhealthy diet based on processed food is likely to promote chronic inflammation in both conditions; hence, appropriate nutrition should be an integral part of the children's therapy. This review discusses dietary models that have a positive impact on patient health.

Increasing trend of childhood type 1 diabetes incidence: 20-year observation from Greater Poland Province, Poland.

AIM: Type 1 diabetes is one of the fastest-growing chronic health conditions. Estimating the incidence rate of childhood type 1 diabetes will allow to aid in adequate planning of health care resources. The study's aim was to assess the incidence rate of type 1 diabetes in children below 15 years of age from Greater Poland (Poland) between 2006 and 2018, and then to compare obtained data to records collected between 1998 and 2003 in pediatric population aged 0-14 years from the same area. METHODS: In this cohort study covering the period from January 1998 to December 2018, data were collected for children and adolescents below 14 years of age with newly diagnosed type 1 diabetes living in Greater Poland. The overall population size was taken from the Statistical Office of Poland. Total, sex-, and age-specific incidence rates per 100,000 person-years were calculated for each calendar year. RESULTS: Over a 20-year period, the incidence rate of type 1 diabetes in children aged 0-14 years rose around 3.6-fold, from 8.4/100,000 in 1998 to 30.8/100,000 in 2018, with the peak incidence recorded in last year of the study. A clear male predominance of type 1 diabetes was seen in all ages. The rate of type 1 diabetes incidence growth was comparable between all age groups, while the highest incidence rate was mostly observed in children aged 5-9 and 10-14 years. CONCLUSIONS: The incidence of type 1 diabetes in children aged 0-14 years is rapidly increasing in Greater Poland.

Ambulatory blood pressure parameters and their association with albuminuria in adolescents with type 1 diabetes mellitus.

BACKGROUND: This study aimed to evaluate the blood pressure (BP) status, including arterial stiffness parameters, hemodynamic indicators, circadian profile, and its association with albuminuria in adolescents with type 1 diabetes mellitus (DM1). METHODS: The analysis included 46 patients, with diabetes duration of 7.38 ± 3.48 years. Ambulatory blood pressure monitoring (ABPM) was conducted using an oscillometric device, the Mobil-O-Graph, which is a Pulse Wave Analysis Monitor. RESULTS: Hypertension (HT) was diagnosed in 31 adolescents (67% of patients), primarily due to isolated nocturnal BP (21 cases, 68% of HT cases). The HT group exhibited significantly increased diastolic load (DL). Pulse wave velocity (PWV, a measure of arterial stiffness) values showed a strong correlation with both peripheral systolic BP (r = 0.954) and central systolic BP (r = 0.838). Additionally, non-dipping status was found in 61% of the HT group. Urinary albumin excretion (UAE) was positively correlated with diastolic BP (particularly nocturnal) peripheral and central BP, DL, heart rate, augmentation index (AIx@75), and nocturnal total vascular resistance (TVR). Diastolic non-dippers exhibited a significant increase in UAE. CONCLUSIONS: Hypertension is a common complication in adolescents with type 1 diabetes mellitus, primarily caused by elevated nocturnal diastolic BP. Albuminuria is mainly associated with diastolic BP, especially during the nocturnal period and in cases of diastolic non-dipping status. The association of UAE with AIx@75 and nocturnal TVR suggests the presence of early-stage vascular disease in diabetic adolescents.

Dietary treatment of type 1 diabetes - once upon a time versus today.

Type 1 diabetes is a disease in which nutrition is an integral part of treatment. The type of recommended diets for therapeutic purposes has changed over the years. Proper metabolic equalization of the disease is an enormous challenge and problem for patients at the same time. This review paper discusses the history of dietary treatment of type 1 diabetes and refers to current dietary recommendations and their impact on the patient's health. The important roles of glycaemic index and glycaemic load are pointed out for proper treatment and slowing of the development of complications. Attention is also paid to the role of dietary education as an integral part of therapeutic management. Continuous progress in the development of technology is of great help to the patient.

Acute kidney injury and diabetic kidney disease in children with acute complications of diabetes.

BACKGROUND: Diabetic ketoacidosis (DKA) and hyperglycaemia without ketoacidosis are common acute complications of diabetes. Their association with acute kidney injury (AKI) and diabetic kidney disease (DKD) was studied. METHODS: The study group consisted of 197 children with type 1 diabetes with average diabetes duration of 8.08 ± 2.32 years. The medical history of the patients was retrospectively reviewed. The number of children with severe hyperglycaemia, DKA and AKI was assessed. The association with the risk of chronic kidney disease (CKD) was analysed. RESULTS: AKI was found in 14% of cases hospitalised for DKA and 8% of cases hospitalised for hyperglycaemia. Patients with AKI showed a significantly increased corrected sodium (141.23 ± 5.09 mmol/L, p = 0.035). Patients with AKI in DKA showed a significant increase in WBC (20.73 ± 8.71 × 103/µL, p = 0.0009). Follow-up analysis after a minimum of 5 years of diabetes revealed that a single episode of DKA was found in 63 patients and a single episode of AKI in 18 patients. Two or more episodes of DKA were found in 18 patients, and nine cases were complicated by AKI. These patients showed a significant increase in urinary albumin excretion (44.20 ± 64.21 mg/24 h), the highest values of eGFR and the worst glycaemic control. CONCLUSIONS: Diabetic children can develop AKI in the course of DKA and hyperglycaemia without ketoacidosis, which is associated with volume depletion and reflected by corrected sodium concentration. AKI in DKA seems to be complicated by stress and inflammation activation. AKI and poor glycaemic control with repeated DKA episodes can magnify the risk of progression to DKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Animal Foetal Models of Obesity and Diabetes - From Laboratory to Clinical Settings.

The prenatal period, during which a fully formed newborn capable of surviving outside its mother's body is built from a single cell, is critical for human development. It is also the time when the foetus is particularly vulnerable to environmental factors, which may modulate the course of its development. Both epidemiological and animal studies have shown that foetal programming of physiological systems may alter the growth and function of organs and lead to pathology in adulthood. Nutrition is a particularly important environmental factor for the pregnant mother as it affects the condition of offspring. Numerous studies have shown that an unbalanced maternal metabolic status (under- or overnutrition) may cause long-lasting physiological and behavioural alterations, resulting in metabolic disorders, such as obesity and type 2 diabetes (T2DM). Various diets are used in laboratory settings in order to induce maternal obesity and metabolic disorders, and to alter the offspring development. The most popular models are: high-fat, high-sugar, high-fat-high-sugar, and cafeteria diets. Maternal undernutrition models are also used, which results in metabolic problems in offspring. Similarly to animal data, human studies have shown the influence of mothers' diets on the development of children. There is a strong link between the maternal diet and the birth weight, metabolic state, changes in the cardiovascular and central nervous system of the offspring. The mechanisms linking impaired foetal development and adult diseases remain under discussion. Epigenetic mechanisms are believed to play a major role in prenatal programming. Additionally, sexually dimorphic effects on offspring are observed. Therefore, further research on both sexes is necessary.

Above 40% of Polish children and young adults with type 1 diabetes achieve international HbA1c target - results of a nationwide cross-sectional evaluation of glycemic control: The PolPeDiab HbA1c study.

BACKGROUND: Youth with type 1 diabetes (T1D) (16-18 y.o.) present worst disease control of all age groups and need structured interventions. Those should be based on unbiased, national-scale outcomes, which have not yet been successfully assessed in Poland. OBJECTIVE: To evaluate the glycemic control in young patients with T1D in Poland. METHOD: All pediatric diabetes care centers and the nine largest centers for adults with T1D were invited to this cross-sectional study, conducted in March 2018. Eligibility was defined as age ≤ 30 years and diabetes duration ≥1 year. Blinded samples of capillary blood and clinical questionnaires were sent to coordinating center, where HbA1c was measured by high-pressure liquid chromatography. RESULTS: Nine adult and 25/28 pediatric centers participated, providing data for 1255 patients (50.8% males), mean age 12.3 years (95%CI:12.1-12.6) for children and 23.2 years (22.9-23.6) for adults; mean diabetes duration 7.1 years (6.8-7.3). This covered ~8% of pediatric population and 2% of 18-30-years-olds with T1D. Mean HbA1c was comparable between children and adults (57 mmol/mol [7.4%], 95%CI:56-57 mmol/mol [7.3-7.4%] vs. 57 mmol/mol [7.4%], 95%CI:56-60 mmol/mol [7.3-7.6%], p = 0.1870). Overall, 45.2% of patients achieved ISPAD target (<53 mmol/mol [<7.0%]). During the month preceding the study, 0.9% of patients experienced severe hypoglycemia and 0.4% suffered ketoacidosis. HbA1c was related to the method of insulin therapy, continuous glucose monitoring use and body weight (p < 0.0001). CONCLUSIONS: In Polish children and young adults with T1D glycemic control expressed as HbA1c is promising in the light of ISPAD guidelines. Our results confirm the known associations between better glycemic control and the use of new technologies and maintaining optimal body weight.

Neuropeptide Y and Peptide YY in Association with Depressive Symptoms and Eating Behaviours in Adolescents across the Weight Spectrum: From Anorexia Nervosa to Obesity.

Neuropeptide Y (NPY) and peptide YY (PYY) are involved in metabolic regulation. The purpose of the study was to assess the serum levels of NPY and PYY in adolescents with anorexia nervosa (AN) or obesity (OB), as well as in a healthy control group (CG). The effects of potential confounders on their concentrations were also analysed. Eighty-nine adolescents were included in this study (AN = 30, OB = 30, and CG = 29). Anthropometric measurements and psychometric assessment of depressive symptoms, eating behaviours, body attitudes, and fasting serum levels of NPY and PYY were analysed. The AN group presented severe depressive symptoms, while the OB group held different attitudes towards the body. The levels of NPY were lower in the AN and OB groups as compared with the CG. The PYY levels were higher in the OB group than in the AN group and the CG. The severity of eating disorder symptoms predicted fasting serum concentrations of NPY. Lower levels of NPY in AN, as well as in OB suggests the need to look for a common link in the mechanism of this effect. Higher level of PYY in OB may be important in explaining complex etiopathogenesis of the disease. The psychopathological symptoms may have an influence on the neurohormones regulating metabolism.

Early kidney damage in diabetic adolescents with increased blood pressure and glomerular hyperfiltration.

BACKGROUND: The early impact of type-1 diabetes mellitus (DM1), increased blood pressure and glomerular hyperfiltration (GHF) on kidney damage in adolescents using two urinary markers of kidney injury - neutrophil gelatinase-associated lipocalin (uNGAL) and transferrin (uTransf) was assessed. METHODS: The study group consisted of 80 adolescents with DM1, of whom 42 were patients with increased blood pressure (IBP), and 38 were patients with normal blood pressure (NBP). Blood pressure was assessed by 24-hour ambulatory bloodpressure monitoring. All patients showed estimated glomerular-filtration rates (eGFRs) above 90 ml/min/1.73m2. The control group consisted of 19 healthy, age and gender-matched adolescents. RESULTS: All diabetic children showed a significant increase in uNGAL (p<0.001). This increase was not related to blood pressure. The uNGAL was elevated in all patients with normal albuminuria, normal eGFR and NBP. The concentration of uTransf was not increased in the entire studied group and was not related to blood pressure. Children with GHF had significantly higher levels of both uTransf (p=0.010) and uNGAL (p<0.001). In patients with GHF, blood pressure was normal. Patients with IBP showed a significantly higher value for triglycerides (r=0.247; p=0.032) and a longer duration of diabetes (r=0.264; p=0.019). CONCLUSIONS: Diabetes is the leading risk factor for early kidney injury. However, increased blood pressure does not lead to kidney damage, at least in the early stage of DM1. The uNGAL is the early indicator of kidney injury and increases in patients with normal albuminuria, normal glomerular filtration and normal blood pressure. Glomerular hyperfiltration seems to be a marker of diabetic-kidney involvement.

Nighttime Hypoglycemia in Children with Type 1 Diabetes after one Day of Football Tournament.

The aim of the study was to investigate factors related to the occurrence of nighttime hypoglycemia after a football tournament in children with type 1 diabetes mellitus. The multicenter study (GoalDiab study) included 189 children and adolescents with type 1 diabetes mellitus, from 11 diabetes care centers in Poland. Hypoglycemia was defined according to the International Hypoglycemia Study Group Statement. We analyzed the data of 95 participants with completed protocols with regards to nighttime hypoglycemia (82% male), aged 11.6 (9.8-14.2) years, diabetes duration 5.0 (2.0-8.0) years. There were 47 episodes of nighttime Level 1 hypoglycemia (≤3.9 mmol/L). Occurrence of clinically important Level 2 hypoglycemia (<3.0 mmol/L) during a game period was positively associated with nighttime hypoglycemia (≤3.9 mmol/L) incident (Odds Ratio=10.7; 95% Confidence Interval: 1.1-100.2; p=0.04). Using Continuous Glucose Monitoring was negatively associated with the occurrence of nighttime hypoglycemia (≤3.9 mmol/L) compared with using glucose meters or Flash Glucose Monitoring (Odds Ratio=0.31; 95% Confidence Interval: 0.12-0.83; p=0.02). The occurrence of clinically important hypoglycemia related to physical activity is associated with the occurrence of hypoglycemia during the night. Continuous Glucose Monitoring is negatively associated with nighttime hypoglycemia after a day of competition.

Assessment of Safety and Glycemic Control During Football Tournament in Children and Adolescents With Type 1 Diabetes-Results of GoalDiab Study.

PURPOSE: To assess glycemic control and safety of children and adolescents with type 1 diabetes participating in a 2-day football tournament. METHODS: In total, 189 children with type 1 diabetes from 11 diabetes care centers, in Poland, participated in a football tournament in 3 age categories: 7-9 (21.2%), 10-13 (42.9%), and 14-17 (36%) years. Participants were qualified and organized in 23 football teams, played 4 to 6 matches of 30 minutes, and were supervised by a medical team. Data on insulin dose and glycemia were downloaded from personal pumps, glucose meters, continuous glucose monitoring, and flash glucose monitoring systems. RESULTS: The median level of blood glucose before the matches was 6.78 (4.89-9.39) mmol/L, and after the matches, it was 7.39 (5.5-9.87) mmol/L (P = .001). There were no episodes of severe hypoglycemia or ketoacidosis. The number of episodes of low glucose value (blood glucose ≤3.9 mmol/L) was higher during the tournament versus 30 days before: 1.2 (0-1.5) versus 0.7 (0.3-1.1) event/person/day, P < .001. Lactate levels increased during the matches (2.2 [1.6-4.0] mmol/L to 4.4 [2.6-8.5] mmol/L after the matches, P < .001). CONCLUSIONS: Large football tournaments can be organized safely for children with type 1 diabetes. For the majority of children, moderate mixed aerobic-anaerobic effort did not adversely affect glycemic results and metabolic safety.

What a type of diabetes is having your patient? Challenges in diagnosing diabetes in children and adolescent - case report.

Diabetes mellitus (DM) is due to either defects in not producing enough insulin by the pancreatic -cells, or defects in insulin action on peripheral tissues. Type 1 diabetes (T1D) is the most common type in childhood, resulted from the autoimmunity directed at the pancre-atic -cells. T1D classically presents in lean children with an acute onset of polyuria, polydipsia, weight loss. We describe the case of a 14-year-old girl with acute onset of DM complicated with diabetic ketoacidosis, appendicitis and pancreatitis which was suspected of having T1D. However, regardless a suggestive patient's phenotype at the disease onset tentative diagnosis of T1D was not confirmed. The case report shows that the overlap of the clinical phenotypes of diabetes displays the diversity of diabetes in young population. Then, diagnostic process must be carefully planned to exclude other diabetes forms and accurately ascertain childhood diabetes type.

miR-487a-3p upregulated in type 1 diabetes targets CTLA4 and FOXO3.

AIMS: Type 1 diabetes (T1D) is an autoimmune disorder caused by the T-cell mediated destruction of the insulin-producing pancreatic beta cells. T1D is a consequence of complex processes, influenced by genetic, epigenetic and environmental factors. MicroRNAs (miRNAs) are small non-coding RNAs that target multiple mRNAs and regulate gene expression. The implication of miRNAs in T1D pathogenesis, as potential modulators of immune response genes, remains poorly defined. The aim of this study was to investigate the expression profile of miRNAs in new onset T1D and the impact of deregulated miRNAs on target genes. METHODS: Total RNA from peripheral blood mononuclear cells of newly diagnosed T1D pediatric patients and age-matched controls was screened for disease-associated miRNAs by a microarray analysis, with subsequent validation by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). miRNA targets were identified by luciferase reporter assays. RESULTS: The microarray analysis revealed 91 deregulated miRNAs (P < 0.05) in T1D group compared to non-diabetic controls. Within this group we observed one upregulated and seven downregulated miRNAs with fold change >2.0. qRT-PCR validation revealed overexpression of miR-487a-3p which has not been previously reported in the context of T1D. Luciferase reporter assays indicated CTLA4 and FOXO3 genes as miR-487a-3p targets. CONCLUSION: Our study suggests that miR-487a-3p might repress CTLA4 and FOXO3 by binding to their 3'UTRs and contribute to the development of T1D.

Autoantibodies against zinc transporter 8 are related to age and metabolic state in patients with newly diagnosed autoimmune diabetes.

AIMS: To assess the prevalence of ZnT8-ab and its correlation to other autoimmune markers and diabetic ketoacidosis occurrence in children and adults with T1DM onset. METHODS: The study included 367 patients (218 children; 149 adults) at the T1DM onset. Selected diabetes-related autoantibodies such as GAD-ab, IA2-ab, ZnT8-ab were tested before the initiation of insulin therapy. Diabetic ketoacidosis was defined as glucose concentration > 13.9 mmol/l, pH < 7.30, concentration of HCO3 < 15 mmol/l, presence of ketone bodies in the blood and urine. RESULTS: The autoantibodies pattern differs in both study groups. Children were mostly positive for two (37.8%) and three (49.5%) autoantibodies, whereas adults for one (32.2%) and two (30.7%). The most frequently detected autoantibodies in youth were ZnT8-ab (81.1%) and IA2-ab (80.7%), while in adults GAD-ab (74.8%). ZnT8-ab (p < 0.0001) titers were significantly higher in children, but adults had higher titer of GAD-ab (p < 0.0001) and IA2-ab (p < 0.0001). Children developed more frequently diabetic ketoacidosis (28.4 vs. 10.7%, p = 0.0002). ZnT8-ab (p = 0.002) and IA2-ab (p = 0.008) were reported mostly in individuals with ketoacidosis. A correlation between the number of positive antibodies and the severity of ketoacidosis was observed (Rs - 0.129 p = 0.014). ZnT8-ab were associated with a greater risk of ketoacidosis independent of gender, age group and the autoantibodies number [OR = 2.44 (95% CI 1.0-5.94), p = 0.04]. CONCLUSIONS: Children are at greater risk of ketoacidosis at the diagnosis of diabetes. ZnT8-ab and IA2-ab are commonly detected in children, while adults have frequently higher titer of GAD-ab. ZnT8-ab are associated with more acute diabetes onset.

FKBP5 polymorphism is associated with insulin resistance in children and adolescents with obesity.

OBJECTIVE: Since metabolic syndrome shares several clinical features with hypercortisolism, it was hypothesised that genes altering individual glucocorticoid (GC) sensitivity might be implicated in pathogenesis of obesity and its adverse outcomes. FKBP5 gene encodes a chaperon protein in the GC receptor (GR) complex, which modulates steroid action upon target genes. Its functional variant, rs1360780, may enhance FKBP5 gene transcription, affect GR signalling and thereby influence the hypothalamo-pituitary-adrenal axis. We investigated the association of rs1360780 with obesity and metabolic characteristics in 250 obese children and adolescents (mean age 12.3±3.6years, BMI ≥95th percentile). METHODS: Anthropometric measurements, body composition, biochemical and hormonal results were analysed. Genotyping of rs1360780 was compared with 568 lean controls. RESULTS: Impaired fasting glucose was present in 8.8%, glucose intolerance in 10.4%, diabetes in 2.8% and dyslipidemia in 28.8% obese individuals. Hypertension was diagnosed in 34 out of 143 patients. No difference was found in FKBP5 polymorphism distribution between subjects with obesity and controls (p>0.05). Stratification by rs1360780 revealed no differences in body mass and composition. However, carriers of the minor allele displayed enhanced insulin resistance (p=0.009) and elevated serum triglyceride (p=0.006), whereas cholesterol, HbA1c, and oral glucose challenge results were similar for all genotypes. Morning ACTH and cortisol did not differ but evening cortisol was higher in minor allele carriers (p=0.039), although this association was lost in logistic regression analysis. CONCLUSION: This study does not support the association of FKBP5 with obesity but demonstrates plausible implication of its variant in susceptibility to obesity-related insulin resistance and hypertriglyceridemia.

Prader-Willi Syndrome - nutritional management in children, adolescents and adults.

Prader-Willi Syndrome is a genetic condition caused by an abnormality of chromosome 15, mostly resulting from a deletion.The prevalence of syndrome in Europe has been reported between 1 in 8,000 to 1 in 45,000 births. Characteristic features of the syndrome include hypotonia, short stature, psychomotor development delay, hypogonadism and progressive, life-threatening obesity. Treatment of Prader-Willi Syndrome consists of intensive rehabilitation, psychologicalcare, speech therapy and also, if patient is fulfilling appropriate criteria, growth hormone treatment. An extremely important element of therapy is also properly planned and implemented nutritional management. Adequate diet prevents the malnutrition in the first stage of life and the development of excessive weight in subsequent years. The aim of this article is to provide practical and accurate guidance on nutritional management and diet therapy for physicians and nutritionists who work with children, adolescents and adults with Prader-Willi Syndrome.

Serum leptin and adiponectin levels in children with type 1 diabetes mellitus - Relation to body fat mass and disease course.

PURPOSE: Leptin and adiponectin are adipokines presenting a wide range of impacts, including glycemic balance regulations. Insulin is one of the main regulators of adipose tissue function. In type 1 diabetes mellitus (T1DM) endogenous insulin secretion is replaced by the exogenous supply, which is not regulated naturally. The aim of the study was to establish serum leptin and adiponectin levels, and their relations to body fat mass and disease course in children with T1DM. MATERIAL/METHODS: The study included 75 children with T1DM and the control group of 20 healthy coevals. All children had estimated serum leptin and adiponectin concentrations, lipid profile, and bioelectrical impedance analysis. RESULTS: Serum leptin concentrations in children with T1DM were not significantly different from the control group (p=0.067, mean values±SD: 3.11±2.98 vs. 5.29±5.06µg/l, respectively), and related positively to body fat mass in both groups. Adiponectin serum concentrations were significantly higher in children with T1DM than in the control group (p<0.001; mean values: 18.82±9.31 vs. 12.10±5.53µg/ml, respectively), and were not related to the body fat content in the study group. Both, leptin and adiponectin, showed no relation to any of the analyzed parameters of the disease course. CONCLUSIONS: Differences observed between children with T1DM and their healthy coevals, when similar in terms of age, body weight, and body fat mass, seem not to depend directly on the disease duration, its metabolic control or insulin supply.

Cumulative effect of IFIH1 variants and increased gene expression associated with type 1 diabetes.

AIMS: IFIH1 (Interferon Induced with Helicase C domain 1) gene encodes a sensor of double-stranded RNA, which initiates antiviral activity. Recent studies have indicated the association of rare and common IFIH1 variants with type 1 diabetes mellitus (T1D). The aim of this study was to investigate whether polymorphisms in the IFIH1 locus are a risk factor for T1D in Caucasian patients from Poland. METHODS: We genotyped 514 T1D patients and 713 healthy control individuals for rs3747517, rs1990760, rs2111485 and rs13422767 variants. Cumulative genetic risk score (CGRS) was calculated using unweighted and weighted approaches. We also examined the expression of IFIH1 gene in a cohort of 90 T1D patients. RESULTS: All studied polymorphisms showed significant association with type 1 diabetes. The risk alleles G of rs3747517, rs2111485, rs13422767 and A of rs1990760 were observed more frequently in T1D group with P values and allelic odds ratio OR (95%CI) < 0.0001, 1.742 (1.428-2.126); 0.001, 1.336 (1.125-1.588); < 0.0001, 1.799 (1.416-2.285); 0.0005, 1.359 (1.144-1.616), respectively. The risk for type 1 diabetes increased with the growing number of the risk alleles. OR (95%CI) for carriers of ≥ 6 risk alleles reached 2.387 (1.552-3.670) for unweighted CGRS and 3.132 (1.928-5.089) for weighted CGRS. Furthermore, IFIH1 gene expression levels in unstimulated peripheral blood mononuclear cells of T1D patients were significantly higher compared to healthy individuals (mean ± SEM mRNA copy number 163.8 ± 15.7 vs. 117.8 ± 7.2; P = 0.046). CONCLUSIONS: This study confirms the association of the IFIH1 locus with susceptibility to T1D in the Polish population. The cumulative effect of rs3747517, rs1990760, rs2111485 and rs13422767 variants on type 1 diabetes risk was observed.

Serum resistin concentrations in children with type 1 diabetes mellitus--negative relation to body fat mass.

INTRODUCTION: Insulin is one of the major factors regulating adipose tissue function. On the other hand, adipocytes secrete adipocytokines that may influence insulin synthesis and action, and are involved in blood glucose regulation. In type 1 diabetes mellitus (t1DM), beta cells function is replaced with exogenous insulin therapy. This raises a question concerning the impact of t1DM on adipose tissue secretory function. The aim of this study was to evaluate one of the adipocytokines, resistin, serum concentrations in relation to body fat mass in children with t1DM. MATERIAL AND METHODS: The study comprised 75 children with t1DM and a control group of 20 healthy coevals. All children had estimated serum resistin concentrations, glycated haemoglobin levels, growth and body weight measurements, and bioelectrical impedance analysis in order to establish body composition. RESULTS: Resistin serum concentrations were significantly lower in children with t1DM vs. controls (median values: 343 vs. 590 pg/mL; mean values ± SD: 577 ± 561 vs. 861 ± 628 pg/mL; p < 0.001), and they negatively correlated with body fat mass (p = 0.022) and age (p = 0.022) in the t1DM group, but not in the control group. Disease duration, glycated haemoglobin levels and insulin dosage revealed no direct statistical relation to resistin levels. CONCLUSIONS: Diminished serum resistin concentrations and a negative correlation between resistin levels and body fat mass in children with type 1 diabetes seem to result from broken physiological adipo-insular regulations, independent of disease duration, its metabolic control and insulin supply.