Prolonged Remission Induced by FENofibrate in children with newly diagnosed type 1 diabetes (PRIFEN): protocol of a randomised controlled trial.

INTRODUCTION: Sphingolipids regulate proinsulin folding, insulin secretion and control beta cells apoptosis. Recent evidence has demonstrated that, among other factors, reduced amounts of sulfatide may be relevant in the development of type 1 diabetes (T1D). Thus, fenofibrate, which activates sulfatide biosynthesis, may prolong remission in subjects with T1D. The aim of the study is to evaluate clinical efficacy of fenofibrate on the maintenance of residual beta-cell function in children with newly diagnosed T1D. METHODS AND ANALYSIS: A total of 102 children aged 10-17 years with newly diagnosed T1D will be enrolled in a double-blind, two-centre randomised, non-commercial, placebo-controlled trial. Subjects who will meet all inclusion criteria will be randomly assigned to receive fenofibrate at a dose of 160 mg or an identically appearing placebo, orally, once daily, for 12 months. The primary endpoint will be the area under the curve of the C-peptide level during 2-hour responses to a mixed-meal tolerance test (MMTT). Secondary endpoints include fasting and maximum C-peptide concentration in the MMTT, parameters of diabetes control and glucose fluctuations, daily insulin requirement, inflammation markers, genetic analysis, safety and tolerance of the fenofibrate ETHICS AND DISSEMINATION: The study protocol was approved by the Bioethics Committee. The results of this study will be submitted to a peer-reviewed diabetic journal. Abstracts will be submitted to international and national conferences. TRIAL REGISTRATION NUMBER: EnduraCT 2020-003916-28.

Pure-protein load for children with type 1 diabetes: is any additional insulin needed? A randomized controlled study.

AIMS: Study in adults with T1D showed that delivery of insulin for pure-protein meals may not be obligatory. The aim of this study was to assess the effects of whey isolate protein drink consisting of 50 g/200 kcal from pure protein on postprandial glycemia (PPG) following with square-wave insulin bolus in comparison with no insulin strategy in T1D children on insulin pumps. METHODS: This was a randomized, double-blind, cross-over study including 58 children with mean: age 14.62 ± 3.64 years. Participants were randomly assigned into two treatment orders: NB-SQ (no bolus on the first day) and SQ-NB (square-bolus on the first day). The primary outcome was PPG during a 5-h follow-up. The secondary outcome was the frequency of hypoglycemia and glycemic variability parameters. RESULTS: PPG [mg/dl] since 150 min of the follow-up was significantly lower when square-wave bolus was delivered (group SQ vs NB); at 150, 180, 210, 240, 270, 300 min: 130.6 versus 154.5 (p = 0.009), 153.4 versus 124.9 (p = 0.004), 151.0 versus 118.7 (p = 0.003), 146.4 versus 114.2 (p = 0.002), 141.2 versus 107.7 (p = 0.001), 131.0 versus 105.1 (p = 0.005). We observed statistically significant difference in overall rate of hypoglycemia < 70 mg/dl between groups SQ versus NB: 6.8% versus 2.5% (p = 0.001). The overall rate of hypoglycemia below 54 mg/dl was < 1% (p = 0.452). CONCLUSIONS: A meal containing 50 g of pure protein may be consumed without additional insulin dose. An additional square-wave bolus may be beneficial in reducing PPG. To avoid hypoglycemia, lower insulin dose should be calculated for 100 kcal from protein than for individual insulin-to-carb ratio.

The emotional well-being of parents with children at genetic risk for type 1 diabetes before and during participation in the POInT-study.

INTRODUCTION: This study examined the emotional impact that parents experience when confronted with an increased genetic risk of type 1 diabetes (T1D) in their child. Population-based screening of neonates for genetic risk of chronic disease carries the risk of increased emotional burden for parents. METHODS: Information was collected using a well-being questionnaire for parents of infants identified as having an increased risk for T1D in a multinational research study. Parents were asked to complete this questionnaire after they were told their child had an increased risk for T1D (Freder1k-study) and at several time points during an intervention study (POInT-study), where oral insulin was administered daily. RESULTS: Data were collected from 2595 parents of 1371 children across five countries. Panic-related anxiety symptoms were reported by only 4.9% after hearing about their child having an increased risk. Symptoms of depression were limited to 19.4% of the parents at the result-communication visit and declined over time during the intervention study. When thinking about their child's risk for developing T1D (disease-specific anxiety), 47.2% worried, felt nervous and tense. Mothers and parents with a first-degree relative (FDR) with T1D reported more symptoms of depression and disease-specific anxiety (p < 0.001) than fathers and parents without a FDR. CONCLUSION: Overall, symptoms of depression and panic-related anxiety are comparable with the German population. When asked about their child's risk for T1D during the intervention study, some parents reported disease-specific anxiety, which should be kept in mind when considering population-based screening. As certain subgroups are more prone, it will be important to continue psychological screening and, when necessary, to provide support by an experienced, multidisciplinary team.

Diabetic ketoacidosis incidence among children with new-onset type 1 diabetes in Poland and its association with COVID-19 outbreak-Two-year cross-sectional national observation by PolPeDiab Study Group.

BACKGROUND: There are several observations that the onset of coronavirus 19 (COVID-19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country-specific healthcare policies, more national-level evidence is needed to provide generalizable conclusions. OBJECTIVE: To compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID-19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020). METHODS: Reference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new-onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily-reported number of COVID-19-related deaths in each region. RESULTS: We recorded 3062 cases of new-onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre- and post-COVID-19 period, we observed a significant increase in the rate of DKA (37.5%-49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID-19 death toll (March/April 2020) (R = .6, p = .0287) and change in T1D incidence (R = .7, p = .0080). CONCLUSIONS: The clinical picture of new-onset children T1D in Poland deteriorated over a 2-year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID-19 epidemic.

Super Bolus: a remedy for a high glycemic index meal in children with type 1 diabetes on insulin pump therapy?-study protocol for a randomized controlled trial.

BACKGROUND: Postprandial hyperglycemia (PPH) is a common clinical problem among patients with type 1 diabetes (T1D), which is related to high glycemic index (h-GI) meals. The main problem is linked to high, sharp glycemic spikes following hypoglycemia after h-GI meal consumption. There is a lack of effective and satisfactory solutions for insulin dose adjustment to cover an h-GI meal. The goal of this research was to determine whether a Super Bolus is an effective strategy to prevent PPH and late hypoglycemia after an h-GI meal compared to a Normal Bolus. METHODS: A total of 72 children aged 10-18 years with T1D for at least 1 year and treated with continuous subcutaneous insulin infusion for more than 3 months will be enrolled in a double-blind, randomized, crossover clinical trial. The participants will eat a h-GI breakfast for the two following days and receive a prandial insulin bolus in the form of a Super Bolus 1 day and a Normal Bolus the next day. The glucose level 90 min after the administration of the prandial bolus will be the primary outcome measure. The secondary endpoints will refer to the glucose levels at 30, 60, 120, 150, and 180 min postprandially, the area under the blood glucose curve within 180 min postprandially, peak glucose level and the time to peak glucose level, glycemic rise, the mean amplitude of glycemic excursions, and the number of hypoglycemia episodes. DISCUSSION: There are still few known clinical studies on this type of bolus. A Super Bolus is defined as a 50% increase in prandial insulin dose compared to the dose calculated based on the individualized patient's insulin-carbohydrate ratio and a simultaneous suspension of basal insulin for 2 h. Our patients reported the best experience with such a combination. A comprehensive and effective solution to this frequent clinical difficulty of PPH after an h-GI meal has not yet been found. The problem is known and important, and the presented solution is innovative and easy to apply in everyday life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04019821.

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.

Increased frequency of severe diabetic ketoacidosis at type 1 diabetes onset among children during COVID-19 pandemic lockdown: an observational cohort study.

INTRODUCTION: On March 11, 2020 the WHO announced a coronavirus disease 2019 (COVID-19) pandemic. Lockdown restrictions, compromised access to medical care and fear of potential exposure to SARS-CoV-2 have forced patients with non-COVID-19 illnesses such as type 1 diabetes (T1D) to stay home. This situation can lead to delay in T1D diagnosis and insulin treatment resulting in rapid progression to diabetic ketoacidosis (DKA) and therefore increased risk of complications and death.  . AIM: The aim of this study was to evaluate the frequency and severity of DKA at the onset of T1D in children diagnosed in our department during COVID-19 pandemic lockdown from March 2020 till May 2020 in comparison to corresponding period of the previous year. . MATERIAL AND METHODS: We collected data of children with newly diagnosed T1D. DKA was defined according to ISPAD guidelines. . RESULTS: The study cohort comprised 34 children in group 2020 and 52 in group 2019 with an average age 9.90 ±4.9 vs. 9.59±4.7 years with mean HbA1c 12.9 ±2.4 vs. 11.5 ±2.2%, respectively. The incidence of DKA was higher by 12% in group 2020 vs. 2019 (52.94% vs 40.38%; p = 0.276).  Regarding the DKA severity (2020 vs. 2019) 32.35% vs. 11.54% were severe (p = 0.026), 17.65 vs. 13% were moderate (p = 0.759), and 2.94 vs. 15.38% were mild (p = 0.081). None of the analyzed patients were COVID-19 positive. CONCLUSIONS: During the COVID-19 pandemic lockdown changes in society and health care system, the DKA rate has increased by 12 percentage points with more severe cases noted in children with newly diagnosed T1D. Regular education of the whole society about the symptoms of diabetes could contribute to faster diagnosis of T1D and reduction of DKA prevalence. .

Nutritional issues in a diabetic patient with Kearns-Sayre syndrome.

SUMMARY: Kearns-Sayre syndrome (KSS) is a multi-system mitochondrial disease with wide clinical presentation. We describe the case of a 16-year-old girl with KSS accompanied by insulin-dependent diabetes, eosinophilic esophagitis (EoE), Fanconi syndrome, insufficiency of parathyroid gland and severe nutritional problems. Based on recent knowledge, ketogenic diet was introduced to improve metabolic and neurological condition, however in our patient we observed its bad consequences. Unresolved nutritional disorders forced us to proceed with esophagogastroduodenoscopy which revealed EoE. PEG procedure was performed and elemental diet with PPI's was introduced leading to general improvement in the patient's health condition. LEARNING POINTS: Nutrition is an important factor in supportive care of patients with KSS. Ketogenic diet in patients affected by mitochondrial diseases and diabetes requires careful selection and monitoring. To the best of our knowledge, this is the first case that shows the coexistence of EoE, insulin-dependent diabetes and KSS.

The additional dose of insulin for high-protein mixed meal provides better glycemic control in children with type 1 diabetes on insulin pumps: randomized cross-over study.

BACKGROUND: Delivery of insulin for high-protein low-fat meals with carbohydrates on the basis of carbohydrates leads to higher late postprandial glycemia. Studies with mixed meals demonstrated lower blood glucose level after dual wave bolus. The objective of our study was to assess the impact of additional dose of insulin in dual wave bolus for high-protein mixed meal on the postprandial glycemia. MATERIALS AND METHODS: We performed a randomized, double-blind, two-way cross-over study, including 58 children with type 1 diabetes, aged 14.7 ± 2.2 years. Participants were randomly assigned into two treatment orders: NORMAL-DUAL or DUAL-NORMAL BOLUS. They consumed standardized high-protein, low-fat meals with carbohydrates. The primary outcome was postprandial glycemia (PPG) based on capillary blood glucose measurements (CBGM). The secondary outcomes were the frequency of hypoglycemia, area under glucose curve, mean amplitude of glycemic excursion (MAGE) and glycemic rise. RESULTS: PPG assessed at 180 min was significantly lower when dual wave bolus was delivered (NORMAL 162 mg/dL [9 mmol/L] vs DUAL 130.0 mg/dL [7.22 mmol/L]; P = .004). There were no differences in CBGM between both groups at 60 and 120 min. We found differences between the groups in MAGE at 120 min (NORMAL 82.86 mg/dL [4.6 mmol/L] versus DUAL 54.76 mg/dL [3.04 mmol/L]; P = .0008). We observed no differences in the number of hypoglycemic episodes in both groups. CONCLUSION: Applying an additional dose of insulin in dual wave bolus for high-protein mixed meal improved PPG. We observed no statistically significant increase in the number of hypoglycemic episodes associated with this intervention.

High incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes among Polish children aged 10-12 and under 5 years of age: A multicenter study.

AIM: Despite its characteristic symptoms, type 1 diabetes (T1D) is still diagnosed late causing the development of diabetic ketoacidosis (DKA). The aim of this study was to estimate the incidence of DKA and factors associated with the development of acidosis at T1D recognition in Polish children aged 0-17. METHODS: The study population consisted of 2100 children with newly diagnosed T1D in the years 2010-2014 in 7 hospitals in eastern and central Poland. The population living in these areas accounts for 35% of the Polish population. DKA was defined as a capillary pH < 7.3, blood glucose > 11 mmol/L. The analyzed data included age, sex, diabetes recognition, pH, glycated hemoglobin (HbA1c), fasting C-peptide, and body mass index standard deviation score (BMI-SDS). RESULTS: We observed DKA in 28.6% of children. There were 2 peaks in DKA occurrence: in children <5 years of age (33.9%) and aged 10-12 (34%). The highest incidence of DKA was noted in children aged 0-2 (48.4%). In the group with DKA, moderate and severe DKA occurred in 46.7% of children. Girls and children <2 years of age were more prone to severe DKA. The multiple logistic regression analysis showed the following factors associated with DKA: age (P = .002), fasting C-peptide (P = .0001), HbA1c (P = .0001), no family history of T1D (P = .0001), and BMI-SDS (P = .0001). CONCLUSIONS: The incidence of DKA is high and remained unchanged over the last 5 years. Increasing the awareness of symptoms of DKA is recommended among children <5 years of age (especially <2 years of age) and aged 10-12. Children <2 years of age and girls were at the highest risk of severe DKA.

Impact of insulins glulisine and aspart on postprandial glycemia after a high-glycemic index meal in children with type 1 diabetes.

OBJECTIVE: According to current knowledge, glulisine insulin (GLU) has a slightly faster onset of action than aspart (ASP) insulin. Therefore, GLU might lead to a better postprandial profile than ASP following the consumption of high-glycemic index (H-GI) meals. The aim of this study was to assess differences in the action of GLU and ASP after the consumption of a H-GI meal in type 1 diabetic children treated with insulin pumps. DESIGN: FIFTY-SIX TYPE 1 DIABETIC CHILDREN OF MEAN AGE 14.72.0 YEARS WERE INCLUDED IN A RANDOMIZED, DOUBLE-BLIND, TWO-WAY CROSSOVER STUDY. THE SUBJECTS WERE ALLOCATED TO ONE OF TWO TREATMENT ORDERS: GLU-ASP and ASP-GLU. They were given a H-GI breakfast for two subsequent days. METHODS: The primary outcome was postprandial glycemia (PPG) based on continuous glucose monitoring system and self monitoring of blood glucose levels during 3 h of follow-up. The secondary outcomes were the frequency of hypoglycemia, glucose area under the curve, mean amplitude of glycemic excursion, and glycemic rise. RESULTS: THERE WERE NO SIGNIFICANT DIFFERENCES BETWEEN THE GROUPS WITH REGARD TO PPG IN THE DETERMINED TIME INTERVALS AS WELL AS WITH RESPECT TO THE SECONDARY OUTCOMES. BETWEEN 60 AND 120MIN AFTER FOOD CONSUMPTION IN BOTH STUDY GROUPS, BLOOD GLUCOSE LEVELS WERE CLOSE TO OR ABOVE 10.0MMOL/L. GLUCOSE PEAKS WERE HIGHER IN THE GLUASP GROUP THAN IN THE ASPGLU GROUP (90MIN: P=0.065; 120 min: P=0.052). Most of the episodes of hypoglycemia were observed after the second hour of follow-up. CONCLUSIONS: No statistically significant difference was found between GLU and ASP with regard to PPG after the consumption of a H-GI breakfast. Neither GLU nor ASP stabilized the glycemic profile after the consumption of a H-GI meal.