Assessment of Skin Autofluorescence and Its Association with Glycated Hemoglobin, Cardiovascular Risk Markers, and Concomitant Chronic Diseases in Children with Type 1 Diabetes.

Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF's association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D). MATERIALS AND METHODS: A total of 348 children with T1D aged 3-18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann-Whitney U test and Spearman correlation. RESULTS: We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27-1.53] vs. 1.20 [1.07-1.30, AU]; p = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all p < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; p = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, p < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43-1.63] vs. 1.40 [1.27-1.53, AU], p = 0.001). CONCLUSION: Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.

Should people with type 2 diabetes treated by multiple daily insulin injections with home health care support be switched to hybrid closed-loop? The CLOSE AP+ randomized controlled trial.

AIM: The study aim was to evaluate the feasibility, safety and efficacy of automated insulin delivery (AID) assisted by home health care (HHC) services in people with type 2 diabetes unable to manage multiple daily insulin injections (MDI) at home on their own. PATIENTS AND METHODS: This was an open label, multicentre, randomized, parallel group trial. In total, 30 adults with type 2 diabetes using MDI and requiring nursing support were randomly allocated to AID or kept their usual therapy over a 12-week period. Both treatments were managed with the support of HHC services. The primary outcome was the percentage time in the target glucose range of 70-180 mg/dl (TIR). Secondary outcomes included other continuous glucose monitoring metrics, glycated haemoglobin (HbA1c) levels, daily insulin doses, body weight, and of quality of life scores, fear of hypoglycaemia and satisfaction questionnaires. RESULTS: Age (69.7 vs. 69.3 years) and HbA1c (9.25 vs. 9.0) did not differ in MDI and AID at baseline. Compared with MDI, AID resulted in a significant increase in TIR by 27.4% [95% CI (15.0-39.8); p < .001], a decrease in time above range by 27.7% and an unchanged time below range of <1%. A between-group difference in HbA1c was 1.3% favouring AID. Neither severe hypoglycaemia nor ketoacidosis occurred in either group. Patient and caregiver satisfaction with AID was high. CONCLUSIONS: AID combined with tailored HHC services significantly improved glycaemic control with no safety issues in people with type 2 diabetes previously under an MDI regimen with HHC. AID should be considered a safe option in these people when lacking acceptable glucose control.

Lisdexamphetamine versus methylphenidate for paediatric patients with attention-deficit hyperactivity disorder and type 1 diabetes (LAMAinDiab): protocol for a multicentre, randomised cross-over clinical trial in an outpatient telemedicine-supported setting.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) affects 5%-10% of paediatric population and is reportedly more common in children with type 1 diabetes (T1D), exacerbating its clinical course. Proper treatment of ADHD in such patients may thus provide neurological and metabolic benefits. To test this, we designed a non-commercial second phase clinical trial comparing the impact of different pharmacological interventions for ADHD in children with T1D. METHODS AND ANALYSIS: This is a multicentre, randomised, open-label, cross-over clinical trial in children and adolescents with ADHD and T1D. The trial will be conducted in four reference paediatric diabetes centres in Poland. Over 36 months, eligible patients with both T1D and ADHD (aged 8-16.5 years, T1D duration >1 year) will be offered participation. Patients' guardians will undergo online once-weekly training sessions behaviour management for 10 weeks. Afterward, children will be randomised to methylphenidate (long-release capsule, doses 18-36-54 mg) versus lisdexamphetamine (LDX, 30-50-70 mg). Pharmacotherapy will continue for 6 months before switching to alternative medication. Throughout the trial, the participants will be evaluated every 3 months by their diabetologist and online psychological assessments. The primary endpoint (ADHD symptom severity, Conners 3.0 questionnaire) will be assessed by a blinded investigator. Secondary endpoints will include HbA1c, continuous glucose monitoring indices and quality-of-life (PedsQL). ETHICS AND DISSEMINATION: The trial is approved by Bioethical Committee at Medical University of Lodz and Polish regulatory agency (RNN/142/22/KE, UR/DBL/D/263/2022). The results will be communicated to the research and clinical community, and Polish agencies responsible for healthcare policy. Patient organisations focused on paediatric T1D will be notified by a consortium member. We hope to use the trial's results to promote collaboration between mental health professionals and diabetes teams, evaluate the economic feasibility of using LDX in patients with both diseases and the long run improve ADHD treatment in children with T1D. TRIAL REGISTRATION NUMBERS: EU Clinical Trials Register (EU-CTR, 2022-001906-24) and NCT05957055.

Incidence of hyperglycaemic disorders in children and adolescents with obesity.

INTRODUCTION: The prevalence of obesity in the paediatric population has increased significantly in recent decades. To date, the rarest metabolic disturbance associated with obesity has been the hyperglycaemia, including diabetes. The aim of the study was to compare the prevalence of hyperglycaemic disorders diagnosed on the basis of (1) the oral glucose tolerance test (OGTT) and (2) the HbA1c value, and to estimate the prevalence of hyperglycaemia in continuous glucose monitoring (CGM) records in adolescents with obesity. MATERIAL AND METHODS: The study included patients aged 9-18 years with obesity (BMI ≥ 95th percentile). The height, body weight, and waist circumference were measured, and the BMI and BMI Z-score were calculated. Sexual maturity was assessed on the Tanner scale. OGTT was performed, and the HbA1c value was measured. Six-day retrospective blinded CGM was performed. RESULTS: In the group of 143 children (mean age 13.4 years), the severity of obesity positively increased with patients age (r = 0.36 and p < 0.0001). Abdominal obesity was found in 93.4% of children. Based on OGTT, 18.8% of the subjects had hyperglycaemic disorders; impaired glucose tolerance was the most common one (16.1%). Impaired fasting glucose was found in 4 patients (2.8%), and type 2 diabetes was found in 2. The mean HbA1c was 5.4%. HbA1c values ranged from 5.7 to 6.4% in 20.3% of the patients, and it did not exceed 6.4% in any patient. In 27.6% of patients with HbA1c 5.7-6.4%, abnormalities in OGTT were observed (IGT 17.25%, IFG 6.9%, DM2 3.45%). There was a significant discrepancy between OGTT results and HbA1c in the diagnosis of hyperglycaemic disorders (diagnosis agreement - 69.92%). In CGM 1.4% of results were above 140 mg/dl. CONCLUSIONS: Hyperglycaemic disorders are diagnosed in nearly 20% of children with obesity. However, there are significant discrepancies in the diagnosis of glucose disturbances using OGTT and HbA1c. Concordance in the diagnosis of hyperglycaemic disorders was achieved only in 70% of patients. CGM may be useful in the diagnosis of pre-diabetes in people with obesity.

Paediatric diabetes care 100 years after insulin discovery - closer to closing the loop but still yearning for the cure.

When more than 25 years ago I started to work with children with type 1 diabetes I hoped (or at some moments even believed!) that at the 100th anniversary of insulin discovery there would be a cure for them and insulin will not be necessary any more. One of the reasons for that I thought so was that during several months of my internship in Paris in 1995, I had the opportunity to see children with type 1 diabetes participating in a promising study in which cyclosporine was tested (we hoped it would stop autoimmune destruction of pancreatic b cells), and later me myself (not having diabetes), together with several other young colleagues from Professor Jerzy Bodalski's team from Lodz, we received subcutaneous insulin in an initial part of a French study testing the usefulness of insulin in pre-diabetes (the idea behind was to initiate immune tolerance). Years passed, and despite the fact that also in the next decades therapies designed to protect insulin secretion (sophisticated, like anti-CD-3 antibodies or T-regulatory cells and more simple, including the very early use of oral insulin), poly-therapies combining drugs with different mechanisms of action, as well as stem cell-derived beta cells have been extensively studied and some of them seemed to be promising, still today in a hospital room, when talking to a parent of a child with newly diagnosed type 1 diabetes I am forced to say that for their small one we do not have any other effective medicine apart from insulin administered by pen or pump [1-3].

Diabetes Related Distress in Children with Type 1 Diabetes before and during the COVID-19 Lockdown in Spring 2020.

Our aim was to compere diabetes-related distress (DD) in young patients with type 1 diabetes mellitus (T1DM) and in their parents before and during the national COVID-19-related lockdown when schools operated on-line. Problems Areas in Diabetes-Child (PAID-Ch), Teen (PAID-T) and Parent (P-PAID-Ch, P-PAID-T) questionnaires in paper version were used to evaluate DD before COVID-19 pandemic (November 2019-February 2020) and during the lockdown (April 2020) the same surveys were performed by phone. We enrolled 76 patients (median age (Q1-Q3): 13.6 (11.8-15.2) years; 21 children, 55 adolescents; T1DM duration 3.7 (1.7-6.8) years). Initial PAID score was lower in teenage boys than in girls (34.0 (24.0-42.0) vs. 44.5 (40.0-50.5), p = 0.003). In teens PAID score decreased significantly during the lockdown (-3.0 (-11.0-3.0), p = 0.018), more in girls than boys (p = 0.028). In children (-3.0 (-14.0-7.0), p = 0.131) and parents PAID did not change (teens' parents: 3.0 (-9.0-10.0), p = 0.376; children's parents: -5.0 [-9.0-1.0], p = 0.227). In the studied group COVID-19 pandemic-related lockdown was associated with decrease in DD in teens with T1DM, particularly in girls, while no significant change in DD was observed in children or parents. DD decrease in teens during the pandemic should attract attention to the potential "rebound" of DD related to return to regular on-site school routine.

Improved Estimation of Glycated Hemoglobin from Continuous Glucose Monitoring and Past Glycated Hemoglobin Data.

Background: Accurate estimation of glycated hemoglobin (HbA1c) from continuous glucose monitoring (CGM) remains challenging in clinic. We propose two statistical models and validate them in real-life conditions against the current standard, glucose management indicator (GMI). Materials and Methods: Modeling utilized routinely collected data from patients with type 1 diabetes from central Poland (eligibility criteria: age >1 year, diabetes duration >3 months, and CGM use between 01/01/2015 and 12/31/2019). CGM records were extracted from dedicated Medtronic/Abbott databases and cross-referenced with HbA1c values; 28-day periods preceding HbA1c measurement with >75% of the sensor-active time were analyzed. We developed a mixed linear regression, including glycemic variability indices and patient's ID (glucose variability-based patient specific model, GV-PS) intended for closed-group use and linear regression using patient-specific error of GMI (proportional error-based patient agnostic model, PE-PA) for general use. Models were validated with either new HbA1cs from closed-group patients or separate patient-HbA1c pool. External validation was performed with data from clinical trials. Performance metrics included bias, its 95% confidence interval (95% CI), coefficient of determination (R2), and root mean square error (RMSE). Results: We included 723 HbA1c-CGM pairs from 174 patients (mean age 9.9 ± 4.4 years and diabetes duration 3.7 ± 3.6 years). GMI yielded R2 = 0.58, with different bias between Medtronic and Abbott devices [0.120% vs. -0.152%, P < 0.0001], and overall 95% CI = -0.9% to +1%, RMSE = 0.47%. GV-PS successfully captured patient-specific variance (closed-group validation: R2 = 0.83, bias = 0.026%, 95% CI = -0.562% to 0.591%, RMSE = 0.31%). PE-PA performed similarly on new patients (R2 = 0.76, bias = -0.069%, 95% CI = -0.790% to 0.653%, RMSE = 0.37%). In external validation GMI, GV-PS, and PE-PA produced 73.8%, 87.5%, and 91.0% predictions within 0.5% (5.5 mmol/mol) from the true value. Conclusion: Constructed models performed better than GMI. PE-PA provided an accurate estimate of HbA1c with fast and straightforward implementation.

Evaluation of Three Lancing Devices: What Do Blood Volume and Lancing Pain Depend On?

BACKGROUND: Globally millions of people with diabetes still prick their fingers to measure blood glucose. The aim of this study was to comprehensively evaluate and to compare three lancing devices set at the minimum ("1") and at the maximum ("5") lancing depth with respect to blood volume (BV) and pain related to lancing. METHODS: Lancing devices tested were A-Glucoject Dual PLUS, B-droplet (both: HTL-Strefa S.A., Poland), and C-Microlet Next (Ascensia Diabetes Care, Switzerland), all used with personal lancets of three sizes 28G, 30G, and 33G. BVs were measured with calibrated capillaries. Pain related to lancing was expressed as a derivative of pain rating with visual analog scale. RESULTS: In 90 participants with diabetes, 360 lancing procedures were performed. Overall, BV and pain were higher for "maximum" compared to "minimum" lancing depth (for both P < .001). Pain differed between devices (P ≤ .001), overall was higher for device A compared to B or C; in paired comparisons differences were significant for the following settings: A > B for 28G/1 and 33G/1, B > C for 30G/1, and A > C for 28G/1, 30G/1, and 33G/1. In aggregated comparison we did not prove a significant effect of lancet size on either BV nor pain (P = .1109, P = .4966, respectively). CONCLUSIONS: BV depended mainly on lancing depth. Pain depended on lancing depth and to some degree on device type. The results may serve as a source of comparative data of lancing devices performance for studies in which other lancing devices and/or lancets would be tested.The study was registered at ClinicalTrials.gov: NCT03479619.

Evaluation of skin autofluorescence as a surrogate of advanced glycation end products accumulation in children and adolescents with normal haemoglobin A1c values.

INTRODUCTION: Skin autofluorescence (sAF) represents tissue accumulation of advanced glycation end products (AGEs) and correlates with cardiovas-cular morbidity and diabetes risk. THE AIM: To assess sAF in Polish children without diabetes and to investigate whether sAF values in children with chronic diseases (but without glucose metabolism disorders) differ from sAF in healthy children. MATERIAL AND METHODS: Children without diseases known to influence sAF results (diabetes, renal failure) and with HbA1c < 5.7% (39 mmol/mol) were includ-ed, and the total study group was divided into two subgroups: with and without chronic conditions. Skin autofluorescence was meas-ured with an AGE Reader (Diagnoptics BV, Groningen, Netherlands). Data were presented as medians; Mann-Whitney U-test, Kruskall Wallis test, and Spearman's correlation coefficients were used in statistical analyses. RESULTS: The study group included 86 children (41 girls; mean age 10.1 ±4.2 years). Median sAF was 1.20 AU (25th-75th centile: 1.06-1.30). There was a positive correlation between sAF and age (R = 0.37, p = 0.0005). Skin autofluorescence values were higher in children with chronic diseases than in healthy children (1.23 AU [25th-75th centile: 1.10-1.40], n = 51 vs. 1.16 AU [1.06-1.26], n = 36, p = 0.0272). CONCLUSIONS: To our knowledge we present the first data on sAF values in Polish children without glucose metabolism disorders. We suggest that larger, homogenous populations of different ages should be studied to determine if and which diseases affect sAF measurements, and to develop pediatric reference values for sAF. This will allow a wider use of sAF measurement in the assessment of cardiovascular risk in the paediatric population.

Artificial Pancreas Systems for People With Type 2 Diabetes: Conception and Design of the European CLOSE Project.

In the last 10 years tremendous progress has been made in the development of artificial pancreas (AP) systems for people with type 1 diabetes (T1D). The pan-European consortium CLOSE (Automated Glu cose Contro l at H ome for People with Chronic Disea se) is aiming to develop integrated AP solutions (APplus) tailored to the needs of people with type 2 diabetes (T2D). APplus comprises a product and service package complementing the AP system by obligatory training as well as home visits and telemedical consultations on demand. Outcome predictors and performance indicators shall help to identify people who could benefit most from AP usage and facilitate the measurement of AP impact in diabetes care. In a first step CLOSE will establish a scalable APplus model case working at the interface between patients, homecare service providers, and payers in France. CLOSE will then scale up APplus by pursuing geographic distribution, targeting additional audiences, and enhancing AP functionalities and interconnectedness. By being part of the European Institute of Innovation and Technology (EIT) Health public-private partnership, CLOSE is committed to the EIT "knowledge triangle" pursuing the integrated advancement of technology, education, and business creation. Putting stakeholders, education, and impact into the center of APplus advancement is considered key for achieving wide AP use in T2D care.

Assessment of Exercise Capacity in Children with Type 1 Diabetes in the Cooper Running Test.

Regular physical activity increases lifespan for those with type 1 diabetes. However, disease-related barriers may deter children from exercise and affect their fitness. This study examined the safety of the Cooper test concerning diabetes-related acute complications in children with type 1 diabetes and their fitness. Blood glucose was recorded before and 0, 30, 60 min after the test. The covered distances were transformed to z-scores based on the national charts. Body mass index, body fat percentage and glycated hemoglobin were measured. The run was completed by 80 individuals (45% boys, age 13.6±2.1 years; diabetes duration 6.3±3.5 years). During the follow-up 11 children reached glucose alert values (3-3.9 mmol/L), 3 presented clinically significant hypoglycemia (<3 mmol/L), none experienced severe hypoglycemia. The covered distance was 1914±298 m, not significantly different from the reference population (z-score -0.12±0.71 vs 0, p=0.12). The study participants were more overweight than general pediatric population in terms of body mass index (z-score 0.48±0.94 vs 0, p<0.001) and body fat percentage (z-score: 0.37±0.85 vs 0, p<0.001). In conclusion, the Cooper test can be safely used in children with diabetes to assess their physical capacity. Youth with type 1 diabetes present fitness similar to healthy children but exhibit increased body mass index and adiposity.

Achieving target levels for vascular risk parameters in Polish school-age children with type 1 diabetes - a single center study.

Background Therapeutic goals have been established to decrease the risk of long-term complications of type 1 diabetes (T1DM). The effects of these guidelines should be constantly evaluated. Hence, the present study examines the frequency at which children with T1DM treated by one of the Polish reference centers complied with the therapeutic targets issued in 2014 by the International Society for Pediatric and Adolescent Diabetes (ISPAD) and by the Diabetes Poland (PTD). Methods A retrospective analysis (years 2011-2014) was performed in patients with T1DM aged 6.5-18 years, with diabetes duration >12 months and no change of insulin regimen within 6 months. Collected data included insulin therapy regimen, weight, height, blood pressure, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and glycated hemoglobin (HbA1c) level from the last hospitalization. Results The records of 447 patients (260 boys, 299 treated with insulin pump) were analyzed. All ISPAD goals were achieved by 123 (27.5%) patients, but only 43 (9.6%) met all PTD targets. Optimal HbA1c was achieved by 224 (50.1%) according to ISPAD criteria (HbA1c<7.5%) and by 87 (19.6%) patients according to PTD (HbA1c≤6.5%). Obesity was diagnosed in 11.6% of the patients; 19.7% of the patients were overweight. In logistic regression, patient age was the only independent predictor of failing to achieve complete T1DM control (p=0.001, OR=1.12 [1.05-1.23]) and optimal HbA1c (p=0.01, OR=1.1 [1.0-1.2]) according to ISPAD guidelines. Moreover, girls had a greater risk of failing body mass index (BMI) targets (PTD: p=0.002, OR=2.16; ISPAD: p=0.0001, OR=3.37) and LDL-C targets (p=0.005, OR=1.8) than boys. Conclusions Overall, control of vascular risk factors in Polish children with T1DM is unsatisfactory. While too few children are achieving the HbA1c target set by PTD, it is possible that such strict national target helps half of the Polish school-age patients achieve ISPAD-issued aim which is more liberal. High prevalence of overweight among children with T1DM warrants initiatives focused not only on glycemic control but also on motivation of patients to lead a healthy lifestyle.

[Hypoglycaemia unawareness in patients with type 1 diabetes].

Hypoglycaemia unawareness, defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms, is an serious problem in type 1 diabetes mellitus. It is often caused by recurrent or severe hypoglycaemia, which leads to the failure of the autonomic nervous system (hypoglycaemia-associated autonomic failure - HAAF). The hypoglycaemia awareness can be restored by avoiding episodes of hypoglycaemia. Management of hypoglycaemia unawareness is complex, and can only be achieved by a multifactorial intervention of clinical care and structured patient education. In patients in whom functional intensive insulin therapy with insulin analogue, continuous subcutaneous insulin infusion using insulin pumps are ineffective in the prevention of hypoglycaemia the implementation of continuous glucose monitoring (CGM) is advisable. CGM systems equipped with low glucose alarms and prediction alarms not only significantly reduce the risk of severe hypoglycaemia, but also significantly reduce the fear of hypoglycaemia and improve the quality of life of patients and their families. The insulin pumps integrated with CGM automatically suspending insulin infusion when glucose is predicted to soon be low (PLGS) should be preferred in patient with hypoglycaemia unawareness. Hypoglycaemia management is complex and should also include structural education. Particular attention should be paid to the management of hypoglycaemia and appropriate use of modern therapy. The hypoglycaemia unawareness is very common among children under the age of 6 years who are unable to observe the early symptoms of hypoglycemia by themselves. This induces a high risk of frequent and severe hypoglycaemia, which can lead to structural changes in the brain, cognitive dysfunctions, poor mental abilities and behavioral disorders later in life.

UVR protection influences fructosamine level after sun exposure of healthy adults.

BACKGROUND: Seasonal variation in glycated hemoglobin levels has been observed, and sun exposure has been considered as one of the factors associated with this relationship. Fructosamine is a short-time marker of blood protein glycation. AIM: We investigated the effect of seven days of sunbathing on blood fructosamine concentration in healthy volunteers using different ultraviolet radiation (UVR) protections. MATERIALS AND METHODS: Participants were assigned to one of three groups: group A - used a UVA and UVB absorbing sunscreen (N = 15), group B - used a UVB absorbing sunscreen (N = 18), and group C - followed uncontrolled sun protection habits (N = 22). RESULTS: Overall, the fructosamine concentration did not change after sun exposure (baseline 248.8 µmol/l, 25-75%: 238.5 to 258.8 µmol/l vs. after 247.3 µmol/l, 25-75%: 234.9 to 261.8 µmol/l, P = 0.6637). Median change of fructosamine differed significantly between groups (A: -1.90 µmol/l, 25-75%: -17.10 to 1.80 µmol/l vs. B: -3.80 µmol/l, 25-75%: -18.50 to 2.40 µmol/l vs. C: +4.05 µmol/l, 25-75%: -3.20 to 22.0 µmol/l; one-way ANOVAP = 0.0277). After age adjustment and combining groups A and B, the difference in change of fructosamine concentration was statistically significant between groups A + B (decrease) vs. group C (increase, P = 0.0193). CONCLUSION: Appropriate sunscreen use during sunbathing resulted in decreased fructosamine concentrations, while inadequate UVR protection resulted in its increase.

Fetal hemoglobin and hemoglobin A1c level among pediatric patients with type 1 diabetes.

INTRODUCTION: Glycated hemoglobin (HbA1c) is used as a cumulative estimate of mean blood glucose levels from the preceding 5-12 weeks. This is the gold standard in assessing glycemic control in patients with diabetes. The ADA criteria for the diagnosis of diabetes, including HbA1c level, contribute to the importance of recognizing any variation pertaining to the HbA1c measurement. HbA1c is often used as a primary endpoint in the interventional studies among patients with diabetes. Thus, knowledge about factors independently to glycemia, affecting HbA1c is clinically useful. AIM OF STUDY: Evaluation variability of fetal hemoglobin (HbF) level among Polish children with diabetes and how it may affect the HbA1c level measurement. MATERIAL AND METHODS: This was a prospective cohort study. A laboratory HbA1c testing was performed for more than 96% of pediatric diabetic patients in the region. In our study we included all consecutive patients aged 2 to 18 years with type 1 diabetes (T1D) and the disease duration longer than one year (555 patients). All patients had HbA1c and HbF measured at three time-points during minimum one-year period. In the same time, clinical data were recorded. The measurements of HbA1c and HbF were performed by means of cation-exchange high-pressure liquid chromatography (HPLC) on a D-10 Dual A2/F/A1c (Bio-Rad Laboratories, Hercules, CA, USA). Statistical analysis was performed using the Statistica 10.0 package (StatSoft, Tulsa, USA). RESULTS: An average age in the observed group was 12.9±3.8 years, diabetes duration 5.6±3.4 years, HbA1c was 7.59±1.33% (59±10.65 mmol/mol). In 78 (14%) patients elevated levels of HbF (>0.8%) were found at each time-point, mean value 1.2±0.45%. Elevated HbF was associated with younger age at examination (p=0.03) and younger age of diagnosis (p=0.01). It was not related to diabetes duration (p=0.21). No correlation between HbA1c and HbF was observed in the study (R=-0.09; p=0.43). CONCLUSIONS: Fetal hemoglobin does not affect HbA1c measurement among pediatric patients with type 1 diabetes older that 2 years.

The Pro12Ala PPARg2 gene polymorphism involves residual C-peptide secretionand BMI in type 1 diabetes.

INTRODUCTION AND AIM: Since insulin resistance is genetically determined and observed in type 1 diabetes, the study was designed to elucidate an involvement of Ala 12 Pro PPARg2 gene polymorphism in residual C-peptide secretion and BMI variation in children with type 1 diabetes. MATERIAL AND METHODS: In 103 patients with type 1 diabetes genetic analysis of PPARg2 polymorphism, C-peptide measurements and evaluation of BMI and clinical parameters were performed. Control group consisted of 109 healthy subjects. RESULTS: In diabetic patients, only three individuals exhibited Ala 12 Ala genotype (2.9%) and 29 patients were heterozygous Ala 12 Pro (28.2%). Interestingly, Ala12+ variants were associated with higher C-peptide levels in 6 th , 12 th and 24 th months after the onset than Pro 12 Pro genotype (0.39±0.24 pmol/mL vs. 0.22±0.14 pmol/mL, P=0.007 and 0.19±0.09 vs. 0.11±0.07, P=0.01 and 0.13±0.09 vs. 0.07±0.05, P=0.021, respectively). Similarly, C-peptide was also significantly increased in patients with history of type 2 diabetes in the first-degree relatives. The observation was even more evident when Ala12+ variants were taken together with family history of type 2 diabetes. Besides, in 24 th and 36 th months after the onset, Ala12+ variants revealed to be associated with higher BMI normalized by age and sex as compared to Pro 12 Pro (0.557±0.84 vs. -0.119±0.73, P=0.001 and 0.589±0.919 vs. 0.066±0.630, P=0.016, respectively). CONCLUSIONS: Thus, it is likely that PPARg2 gene polymorphism and/or the genetically determined insulin resistance may be associated with residual C-peptide secretion and involve excessive BMI in type 1 diabetes.

The impact of having siblings - analysis of "hygiene theory" of chronic diseases in patients with type 1 diabetes in population of the Lódz region Hygiene theory and type 1 diabetes.

INTRODUCTION: In the recent years there has been a significant increase in the incidence of the type 1 diabetes mellitus. Therefore, numerous studies are underway to evaluate the possible factors underlying this trend. Some studies suggest that better sanitary conditions and lack of contact with microorganisms might be important, thus increasing the risk of disease in firstborns. Moreover, siblings could play an important role in the transmission of pathogens, which, by stimulating the immune system, may prevent the development of atopic and autoimmune diseases including such as type 1 diabetes. Current data, however, are still inconclusive. PURPOSE: The aim of the study was to evaluate the effect of having siblings on the incidence of type 1 diabetes among children and adults. MATERIALS AND METHODS: A group of 469 patients with type 1 diabetes was selected. The study population was composed of 245 adults and 224 youth patients. Information from Outpatient Diabetologic Departments database was gathered. Data such as age at the diagnosis of diabetes, sex of siblings, number and birth order were analyzed. RESULTS: In the studied population, 4.5% were only children, and 30.3% patients came from large families. In the group of type 1 diabetic patients 39.7% were firstborns and this proportion was comparable to the group of healthy subject. The highest proportion of firstborns was noted in the group that was diagnosed after 18 years of age (45,1%) compared to the group that was diagnosed between 10 and 14 (29,1%) (p<0.05). Type 1 diabetic patients that were not firstborns much more often had older siblings of the opposite sex than the same sex. CONCLUSIONS: he firstborns in the population of type 1 diabetes from the Lódz region did not outnumber the healthy subjects. Significantly higher proportion of firstborns in the group that was diagnosed after 18 years of age compared to the group that was diagnosed between 10 an 14 years was noted.

Effect of Insulin Dilution on Lowering Glycemic Variability in Pump-Treated Young Children with Inadequately Controlled Type 1 Diabetes.

BACKGROUND: We investigated whether in young children with inadequately controlled type 1 diabetes and technical problems with continuous subcutaneous infusion of insulin at 100 units/mL the switch to insulin diluted to 10 units/mL (U10) can limit technical problems and improve glycemic control. SUBJECTS AND METHODS: Diluted U10 insulin was started in three children 3.8, 3.2, and 1.3 years old with a hemoglobin A1c (HbA1c) level (mean±SD) of 8.1±0.17% (65±1.7 mmol/mol) and insulin dose of 8.80±2.93 units/day. Patients were evaluated with continuous glucose monitoring (iPro™2; Medtronic Minimed, Northridge, CA) and a quality of life questionnaire (PedsQL™; www.pedsql.org/ ) and surveyed for pump-related problems at baseline and after 3 and 9 months of U10 insulin therapy. RESULTS: Continuous glucose monitoring records showed that glycemic variability assessed by SD and M100 decreased significantly (P=0.0085 and P=0.0482, respectively). HbA1c levels dropped to 7.3±1.00% (56±11.0 mmol/mol) after 3 months and to 6.7±0.55% (50±6.1 mmol/mol) after 9 months (P=0.12). Technical difficulties were minimized. CONCLUSIONS: These results suggest that the use of U10 insulin decreases glycemic variability and improves hampered pump therapy in young children with inadequately controlled type 1 diabetes.