Long-term clinical outcomes and management of hypertriglyceridemia in children with Apo-CII deficiency.

BACKGROUND AND AIM: APO CII, one of several cofactors which regulate lipoprotein lipase enzyme activity, plays an essential role in lipid metabolism. Deficiency of APO CII is an ultra-rare autosomal recessive cause of familial chylomicronemia syndrome. We present the long-term clinical outcomes of 12 children with APO CII deficiency. METHODS AND RESULTS: The data of children with genetically confirmed APO CII deficiency were evaluated retrospectively. Twelve children (8 females) with a mean follow-up of 10.1 years (±3.9) were included. At diagnosis, the median age was 60 days (13 days-10 years). Initial clinical findings included lipemic serum (41.6%), abdominal pain (41.6%), and vomiting (16.6%). At presentation, the median triglyceride (TG) value was 4341 mg/dL (range 1277-14,110). All patients were treated with a restricted fat diet, medium-chain triglyceride (MCT), and omega-3-fatty acids. In addition, seven patients (58.3%) received fibrate. Fibrate was discontinued in two patients due to rhabdomyolysis and in one patient because of cholelithiasis. Seven (58.3%) patients experienced pancreatitis during the follow-up period. One female experienced recurrent pancreatitis and was treated with fresh frozen plasma (FFP). CONCLUSIONS: Apo CII deficiency is an ultra-rare autosomal recessive condition of hypertriglyceridemia associated with significant morbidity and mortality. Low-fat diet and MCT supplementation are the mainstays of therapy, while the benefit of TG-lowering agents are less well-defined.

Evaluation of sarcopenia and phase angle in elderly patients with Parkinson's Disease.

PURPOSE: To investigate sarcopenia and related factors and to determine the disease-specific phase angle (PhA) cut-off score in detecting sarcopenia in elderly patients with Parkinson's Disease (PD). METHODS: This cross-sectional study was conducted with 89 participants. The Mini-Nutritional Assessment (MNA), the Eating Attitude Test-10 (EAT-10), the Physical Activity Scale for The Elderly (PASE) questionnaire and the Hoehn-Yahr scale have been used. Additionally, anthropometric measurements were performed. The diagnosis of sarcopenia was based on the new consensus published by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). PhA has been performed by Bioelectrical Impedance Analysis (BIA) with Tanita MC 780®. RESULTS: The mean age was of the participants 68.9 ± 6.4 years, and 57.3% were male. The prevalence of sarcopenia was 12.3%. PhA, malnutrition, age, disease severity, low calf circumference (CC), low body mass index (BMI), the difference between the pre-diagnosis and current weight loss, dopaminergic treatment, and low PASE score were associated with sarcopenia. The cut-off value of the PhA in terms of the ability to identify sarcopenia was <4.5o with a sensitivity of 53.3% and a specificity of 93.2% (p = 0.001). When we grouped the PhA of the patients according to this cut-off score, it was seen that 14.6% of them were sarcopenic. Age, disease severity, PASE score and hand grip strength were significantly related to both sarcopenia and PhA. CONCLUSION: It is important to be aware of sarcopenia and related factors at an early stage in Parkinson's patients. Because of disease-related symptoms, it may be more appropriate to use a disease-specific PhA cut-off score in the definition of sarcopenia.

Psychometric properties and factor structure of the diabetes eating problem survey- revised (DEPS-R) among adults with type 1 diabetes mellitus.

BACKGROUND AND OBJECTIVE: Although many studies on the Diabetes Eating Problem Survey-Revised (DEPS-R) in adolescents with type 1 diabetes mellitus (T1D), the number of studies validating this questionnaire in adults with T1D is limited. Therefore, this study aimed to examine the factor structure of the Turkish version of the DEPS-R in adults with T1D and internal consistency and construct validity. METHODS: A total of 100 patients with T1D, ages 18-50 years, completed the DEPS-R and EDE-Q. In addition to tests of validity, confirmatory factor analysis was conducted to investigate the factor structure of the 6-item Turkish version of DEPS-R. RESULTS: The Cronbach's alpha coefficient of the DEPS-R Turkish version was 0.77, suggesting good internal consistency. The median (IQ) DEPS-R score was 15.0 (13.0) among all participants. DEPS-R score was significantly correlated with BMI (r = 0.210; p < 0.05) and EDE-Q (r = 0.586; p < 0.01). There was no correlation between the HbA1c values of participants and neither EDE-Q nor DEPS-R scores. The confirmatory factor analysis results show that the three-factor model was a good fit. CONCLUSION: A short, self-administered diabetes-specific screening tool for disordered eating behavior is recommended be used routinely in the clinical care of adults with T1D, and Turkish version of DEPS-R has acceptable internal consistency and construct validity in adults with T1D. LEVEL OF EVIDENCE: Level V, descriptive study. CLINICALTRIALS: gov registration number NCT05346679/ 21.04.2022 (retrospectively registered).

Local complications of insulin administration sites and effect on diabetes management.

BACKGROUND: Administration of insulin may be associated with substantial cutaneous adverse effects, such as lipoatrophy and lipohypertrophy (LH), which can cause glycemic excursions above and below the target levels for blood glucose. Our aim was to evaluate the effect on compliance with the use of insulin administration site, dermatological complications and diabetes management in children with type 1 diabetes (T1D). METHODS: Patients aged 0 - 21 years who were followed up with the diagnosis of T1D for at least one year were included. A 14-question survey including demographic characteristics and a subjective opinion of skin-related complications of insulin administration was given. Data were obtained from the medical records to evaluate the effect of dermatological complications on diabetes management. This study was checked with the STROBE checklist. RESULTS: Two hundred and fifty-four patients were included and 53% of these were female. The mean age was 14.9 ± 4.7 years and the duration of T1D was 7.3 ± 4.1 years. The mean HbA1c level was 8 ± 1.4% and the mean total insulin dose was 0.84 ± 0.25 units/kg/day. More than half of the individuals (57%) were receiving multiple daily injections (MDI) and 43% were on insulin pump therapy (IPT). Of the participants, 11.8% reported LH, 7.5% wound, 21.7% allergy, 55.5% bleeding, 41.3% bruising and 47.2% pain. LH rates varied significantly by regimen, 17.1% in MDI and 4.6% with IPT (p = .001). Those with LH were using higher median doses of insulin (0.97 U/kg/day) than those who did not (0.78 U/kg/day; p = .016). LH was reported more frequently (18.3%) in patients with frequent hypoglycemia (p = .007). Positive correlation between BMI-SDS and LH in patients aged <18 years was found (p = .043). LH rates by site were: right arm 20.8%, left arm 26.4%, right abdomen 26.4%, left abdomen 22.6% and 1% in the right and left leg. CONCLUSIONS: Local complications of insulin therapy are common in young patients with T1D. The complication with the most impact on metabolic control was LH, present in nearly 12% of patients. Users of IPT have a significantly lower risk of LH. The results emphasise the importance of individualised education for young T1D patients and their families about injection site preference and rotation techniques. RELEVANCE TO CLINICAL PRACTICE: The diabetes team should check the insulin administration sites of children with type 1 diabetes at each visit and provide repeated education about the dermatological complications of insulin.

Does minimed 780GTM insulin pump system affect energy and nutrient intake?: long-term follow-up study.

OBJECTIVE: We evaluate the energy and nutrient intake of children, adolescents, and young adults with type 1 diabetes (T1D) who started to use automated insulin delivery (AID) systems before the transition and during follow-up for 6 months in a real-world setting. RESEARCH DESIGN AND METHODS: Twenty-nine people with T1D (PwD) who started to use MiniMed 780GTM participated in the study. Participants' 3-day food diaries and glycemic outcomes were analyzed at baseline and after (the 3rd and 6th month) switching to an advanced hybrid closed-loop system (a-HCL). RESULTS: Mean carbohydrate, protein, and fat intake (energy %) at baseline were 49.1 ± 4.5, 17.8 ± 2.3, and 33.0 ± 3.9, respectively, and there were no statistically significant differences during the follow-up period. However, low fiber (<14 g/1000 kcal) and high saturated fat (>10 energy %) intake in PwD, both baseline and follow-up period. The median auto-correction bolus ratio was 14.0 (9.5)% at auto mode after 14 days, 18.0 (11.0)% at the 3rd month, and 19.0 (7.5)% at the 6th month (p < 0.05). A negative correlation was present between auto-correction boluses with TIR in both the 3rd (r:-0.747, p < 0.01) and 6th month (r:-0.395, p < 0.05). A negative correlation was present between auto-correction boluses with TIR in both the 3rd (r:-0.747, p < 0.01) and 6th month (r:-0.395, p < 0.05). CONCLUSIONS: a-HCLS systems offer better glycemic control. Using the Minimed 780 GTM insulin pump system didn't change the energy and nutrient intake of PwD. This real-world follow-up study suggests that children, adolescents, and young adults with T1D consume saturated fat above and fiber intake lower than recommendations independent of the use of a-HCLS. CLINICAL TRIALS REGISTRATION NUMBER: NCT05666596.

Frequently Asked Questions and Evidence-Based Answers on Medical Nutritional Therapy in Children with Type 1 Diabetes for Health Care Professionals

Medical nutrition therapy is a cornerstone in type 1 diabetes management and is based on the principles of healthy eating. The recommendations presented are valid for all children and their families. A number of frequently asked questions will be addressed in this article. Although carbohydrates are the main nutrient that affects postprandial blood glucose in individuals with type 1 diabetes, intake of carbohydrates (type and amount), protein and fat content of the meal, and glycemic index affect the postprandial glycemic response. In recent years, the relative increase in studies about Ramadan fasting for individuals with type 1 diabetes has indicated that health professionals should be informed about this issue. The difficulties in nutritional management of preschool children should be solved with a professional approach. The increasing frequency of celiac disease in people with type 1 diabetes and an increasing interest in a gluten-free diet for non-celiac reasons (popular diet trends for weight loss or healthy eating) further complicate diabetes management. This review provides evidence-based approaches to frequently encountered problems on medical nutrition therapy in children and adolescents with type 1 diabetes.

Novel Modified Algorithm for High Fat/High Energy Density Meal in Type 1 Diabetes: Less Hypoglycemia

Objective: This aim of this study was to investigate the effect of additional insulin dosing for high fat/high energy density mixed meal over 12 hours. Methods: In this single-center, non-blinded, randomized, cross-over study, a high fat/high energy density test meal was used to study the impact on glycemic response of either carbohydrate counting (CC) on the first day and the Pankowska algorithm (PA) on the second test day. The two methods were compared in 20 adolescents with type 1 diabetes (T1D), aged 9-18 years, using insulin pump therapy and continuous glucose monitoring on postprandial early (0-120 min), late (120-720 min), and total (0-720 min) glycemic response. Results: There was no difference between groups in the duration of normoglycemia in the early period. Postprandially, 50% of patients developed hypoglycemia using the PA at a median of 6.3 (5.6-7.9) hours and the PA was subsequently modified for the remaining ten patients. Area under the curve (AUC) for the early period decreased non-significantly in the CC group, indicating less normoglycemia. No significant difference was found in the AUC of the PA (no hypoglycemia n=4) and modified PA groups (no hypoglycemia n=6) over the whole period (0-12 hours). AUC for level 2 hyperglycemia was statistically greater in the PA-no hypoglycemia patients compared to modified PA-no hypoglycemia patients. Conclusion: There were inter-individual differences in glycemic response to high fat/high energy density meals. An individualized approach to insulin dosing by evaluating food diary and postprandial glucose monitoring appears to be optimal for children and adolescents with T1D.

The Effect of the SARS-CoV-2 Pandemic on Presentation with Diabetic Ketoacidosis in Children with New Onset Type 1 Diabetes Mellitus

Objective: Diabetic ketoacidosis (DKA) is a life-threatening, acute complication of type 1 diabetes mellitus (T1DM). Infection is the most common precipitating factor for DKA, being responsible for more than 50% of such complications. The frequency and severity of DKA in children with T1DM, before and during the coronavirus disease 2019 outbreak were evaluated and compared with pre-pandemic presentation and severity rates. Methods: In total, 199 patients younger than 18 years were included in the study. Patients were divided into two groups: the Coronavirus disease-2019 (COVID-19) pandemic group (new onset T1DM presenting from March 2020 to March 2021; the control group included new onset T1DM from March 2016 to March 2020. Results: The rate of DKA at presentation was similar (p=0.393) during the pandemic period (58.3%) compared to the pre-pandemic years (44.8-64.3%). Although the percentage of DKA was similar, the rate of severe DKA in the COVID-19 group was higher than previous years. Although not significant, the duration of diabetes symptoms was longer in the COVID-19 period than the previous years. Conclusion: This study suggests that the rate of severe DKA, but not the overall rate of DKA, has increased during the COVID-19 pandemic compared to the prior four years. This may be due to the behavior of the parents of sick children and the limited access to the healthcare system. Despite this limited access, parental concern may have been sufficiently high to seek medical attention for their children, avoiding an increased frequency of DKA as the first presentation of new-onset T1DM.

Continuous Glucose Monitoring Systems and the Efficacy of Acarbose Treatment in Cystic Fibrosis-related Dysglycemia.

Early detection of glycemic dysregulation and optimization of glycemic control at cystic fibrosis related diabetes (CFRD) is associated with improved pulmonary function and decreased mortality. The standard 2-hour oral glucose tolerance test (OGTT) is the current routine screening test for CFRD. However, hyperglycemia can be detected by continuous glucose monitoring systems (CGMS) in patients with normal OGTT evaluation. High-dose acarbose is an important alternative, in the treatment of glycemic dysregulation especially accompanied by hypoglycemia. A 7-year-old boy with cystic fibrosis (CF) presented with hyperglycemia. Hypoglycemia (29 mg/dL) and hyperglycemia (400 mg/dL) were demonstrated by OGTT and intermittent CGM (iCGMS). Thickener was added to nutritional solutions and acarbose was initiated as 3x12.5 mg /dose and increased to 6x25 mg without any side effects. On the 20th day of treatment, glycemic dysregulation was resolved. In the early detection of CFRD, screening with OGTT after the age of 10 is insufficient; therefore, routine use of continous or intermittent glucose monitoring systems should be considered. In addition, in CFRDs with severe hypoglycemia, acarbose is an important alternative in the high and increased dose range.

Initial Basal and Bolus Rates and Basal Rate Variability During Pump Treatment in Children and Adolescents

Objective: Pump-treated children with type 1 diabetes (T1DM) have widely differing basal insulin (BI) infusion profiles for specific periods of the day. The pattern of BI requirements depends on the timing and magnitude of cortisol and growth hormone secretion within each age group. In adolescents and young adults, a decreased insulin sensitivity is seen, particularly in the early morning (dawn phenomenon) and to a lesser extent, in the late afternoon (dusk phenomenon). Different approaches exist for the inititation of basal rates. However, there is a lack of evidence-based recommendation, especially in young children. Usually the basal rates are set equally throughout day and night or the day is divided into tertiles. The aim of this study was to analyze the change of the initial, equally distributed, BI rates over the first year of standard insulin pump therapy. Methods: A total of 154 patients with T1DM, aged between 0 and <21 years at diagnosis, from a single center were documented. Patients were divided into five age groups according to age at pump initiation: group 1, <5 years (n=36); group 2, 5-8 years (n=20); group 3, 8-15 years (n=74); group 4, 15-18 years, (n=19); and group 5, >18 years, (n=5). Distribution of hourly basal rates at the initiation of the pump and at the end of first year were evaluated. Results: Median (range) age and diabetes duration was 14.46 (1.91-26.15) and 7.89 (1.16-17.15) years, respectively. Forty-four percent were male, 56% were female. Mean total insulin dose/kg in the whole cohort at the initiation and after one year of pump therapy was 0.86±0.23 U/kg and 0.78±0.19 U/kg, respectively and differed significantly between each age group (p<0.001; p<0.001). Mean daily basal rate/kg showed significant differences between the five groups (p<0.001). Circadian distribution of BI differed markedly among the five age groups. Conclusion: At the initiation of insulin pump therapy, circadian profiles by age group should be taken into account in pediatric patients to optimize basal rate faster and more easily.

The Value of Telemedicine for the Follow-up of Patients with New Onset Type 1 Diabetes Mellitus During COVID-19 Pandemic in Turkey: A Report of Eight Cases

The current Coronavirus disease-2019 (COVID-19) pandemic has forced health care teams to look for alternative approaches to manage a great number of children with diabetes, not only in rural but also in urban locations. The aim was to assess the provision of information about follow-up of new-onset pediatric type 1 diabetes (T1D) patients, and to investigate the integration of telemedicine into routine clinical care in the long term. The changes in coefficient of variation (CV), standard deviation and percentages of time in range (TIR), time below range (TBR) and time above range were evaluated in eight children with new-onset T1D, diagnosed during the COVID-19 pandemic. The study period was two-months of follow-up using a telemedicine system. Median follow-up time was 51 (24-66) days. Two of the patients were using low glucose suspend system and six were on multiple daily injection therapy. Target TIR values were achieved in seven patients in the last televisit and, in line with recent guidelines, a TBR <70 mg/dL (<3.9 mmol/L) (level 1 hypoglycemia) of <4% and a TBR <54 mg/dL (<3.0 mmol/L) (level 2 hypoglycemia) of <1% were achieved in all patients. Seven patients achieved a CV of <36% at their last televisit. Telemedicine as an alternative follow-up tool during unusual circumstances such pandemics, even in countries where it is not routinely used, could be beneficial to achieve optimum glycemic control in patients with new-onset T1D.

Exploring emotional dysregulation characteristics and comorbid psychiatric disorders in type 1 diabetic children with disordered eating behavior risk.

OBJECTIVE: To investigate emotional dysregulation and psychiatric comorbidities associated with DEB-risk in children with type 1 diabetes mellitus (T1DM). METHODS: A total of 75 children with T1DM aged between 8 and 19 were evaluated by K-SADS-PL to assess psychiatric diagnosis. DEB-risk was evaluated via Diabetes Eating Problem Survey-Revised (DEPS-R). Besides, all participants completed the Childhood Depression Inventory (CDI), Difficulties in Emotion Regulation Scale (DERS), and The State-Trait Anxiety Inventory (STAI). RESULTS: DEPS-R-positive (≥20) was detected in 28% of the participants. The only diagnostic difference was a significantly higher frequency of ED in DEPS-R-positive than DEPS-R-negative (OR = 8.5, CI = 1.94-37.1, p = .004). DEPS-R-positive cases had significantly higher scores of the CDI, STAI, DERS, and the subscales of Goals, Impulse, and Strategies of DERS (CDI U = 266.500, p = .001; STAI U = 288.500,p = .001; DERS U = 229.000, p = .001, Goals U = 283.500, p = .008, Impulse U = 274.000, p = .005, Strategies U = 281.500, p = .007). In stepwise linear regression analysis, STAI-state and DERS scores significantly determined DEB-risk (STAI: ß = 0.363, t(60) = 2.33, p = .02, DERS: ß = 0.240, t(60) = 4.14, p < .001). CONCLUSION: This cross-sectional study showed that DEPS-R-positive cases have an 8.5-fold increased risk for ED. DEPS-R-positive ones have difficulties in regulating their emotions and they are incapable of accessing emotion regulation strategies, engaging in goal-directed behavior while under difficult emotions, and impulse control. It can be beneficial for child psychiatrists to screen first for ED in DEPS-R-positive cases who are referred by child endocrinologist. They should also take into consideration anxiety levels and problems in emotion dysregulation in the DEPS-R-positive cases.

Effectiveness of Continuous Subcutaneous Insulin Infusion Pump Therapy During Five Years of Treatment on Metabolic Control in Children and Adolescents with Type 1 Diabetes Mellitus

OBJECTIVE: To compare continuous subcutaneous insulin infusion (CSII) therapy with multiple daily insulin (MDI) therapy on metabolic control in children and adolescents with type 1 diabetes mellitus (T1DM) over the long term. METHODS: Fifty-two T1DM patients treated with CSII and monitored for at least one year prior to and at least five years following CSII were included. Thirty-eight age and sex-matched MDI controls with a 5-year follow up were recruited. RESULTS: Mean age of the subjects, duration of diabetes and CSII therapy were 17.0±4.8 years, 10.7±2.8 years and 7.7±1.5 years respectively. Mean hemoglobin A1c (HbA1c) in the year prior to CSII, during the first year of treatment and after 5 years of CSII were 7.3±1% (56 mmol/mol), 7.0±0.7% (53 mmol/mol) and 7.8±1.3% (62 mmol/mol) respectively. Initial and 5-year mean HbA1C levels of controls were 7.9±1.08% and 8.6±1.8%. Mean HbA1c values were significantly lower in those receiving CSII therapy throughout follow-up. Basal and total insulin doses were significantly lower in the CSII group at all times. HbA1c was compared between subjects by age (0-5, 6-11 and 12-18 years) with no significant difference between them. CONCLUSION: Although CSII mean HbA1c values exceeded accepted good metabolic control limits after 5 years, CSII produces better HbA1c control at all times and in all age groups compared to MDI.

Reliability and Validity of the Diabetes Eating Problem Survey in Turkish Children and Adolescents with Type 1 Diabetes Mellitus.

OBJECTIVE: The aim of this study was to show the reliability and validity of a Turkish version of Diabetes Eating Problem Survey-Revised (DEPS-R) in children and adolescents with type 1 diabetes mellitus. METHODS: A total of 200 children and adolescents with type 1 diabetes, ages 9-18 years, completed the DEPS-R Turkish version. In addition to tests of validity, confirmatory factor analysis was conducted to investigate the factor structure of the 16-item Turkish version of DEPS-R. RESULTS: The Turkish version of DEPS-R demonstrated satisfactory Cronbach's ∝ (0.847) and was significantly correlated with age (r=0.194; p<0.01), hemoglobin A1c levels (r=0.303; p<0.01), and body mass index-standard deviation score (r=0.412; p<0.01) indicating criterion validity. Median DEPS-R scores of Turkish version for the total samples, females, and males were 11.0, 11.5, and 10.5, respectively. CONCLUSION: Disturbed eating behaviors and insulin restriction were associated with poor metabolic control. A short, self-administered diabetes-specific screening tool for disordered eating behavior can be used routinely in the clinical care of adolescents with type 1 diabetes. The Turkish version of DEPS-R is a valid screening tool for disordered eating behaviors in type 1 diabetes and it is potentially important to early detect disordered eating behaviors.

Effects of carbohydrate counting method on metabolic control in children with type 1 diabetes mellitus.

OBJECTIVE: Medical nutritional therapy is important for glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM). Carbohydrate (carb) counting, which is a more flexible nutritional method, has become popular in recent years. This study aimed to investigate the effects of carb counting on metabolic control, body measurements and serum lipid levels in children and adolescents with T1DM. METHODS: T1DM patients aged 7-18 years and receiving flexible insulin therapy were divided into carb counting (n=52) and control (n=32) groups and were followed for 2 years in this randomized, controlled study. Demographic characteristics, body measurements, insulin requirements, hemoglobin A1c (HbA1c) and serum lipid levels at baseline and at follow-up were evaluated. RESULTS: There were no statistically significant differences between the groups in mean HbA1c values in the year preceding the study or in age, gender, duration of diabetes, puberty stage, total daily insulin dose, body mass index (BMI) standard deviation score (SDS) and serum lipid values. While there were no differences in BMI SDS, daily insulin requirement, total cholesterol, low-density lipoprotein and triglyceride values between the two groups (p>0.05) during the follow-up, annual mean HbA1c levels of the 2nd year were significantly lower in the carb counting group (p=0.010). The mean values of high-density lipoprotein were also significantly higher in the first and 2nd years in the carb counting group (p=0.02 and p=0.043, respectively). CONCLUSION: Carb counting may provide good metabolic control in children and adolescents with T1DM without causing any increase in weight or in insulin requirements.