Use of Continuous Glucose Monitoring to Evaluate Postprandial Response to Raw Cornstarch Supplementation in Adult Glycogen Storage Disease Type I

The study is designed as an observational study. Participants will be enrolled at the Unit of Diabetology of the University Hospital "Federico II" in Naples, Italy. After providing written informed consent, each participant will undergo the following assessments, all of which are part of clinical management of patients with hepatic glycogen storage disease and will be performed at the Unit of Diabetology of the University Hospital "Federico II" in Naples: * anthropometric measurements: body weight, height, waist circumference, and hip circumference; * body composition assessment by bioelectrical impedance analysis (BIA) using the QUANTUM V Segmental bioimpedance analyzer to obtain resistance, reactance, and phase angle. These parameters will subsequently be analyzed using dedicated software to estimate fat-free mass (FFM), fat mass (FM), total body water (TBW), intracellular and extracellular water, and skeletal muscle mass; * assessment of resting energy expenditure and substrate oxidation by indirect calorimetry (COSMED calorimeter) using a ventilated hood system equipped with an infrared analyzer for carbon dioxide production (VCO₂) and a zirconium cell analyzer for oxygen consumption (VO₂); * handgrip strength test for the evaluation of muscle strength; * biochemical profile assessment, including fasting plasma glucose, glycated hemoglobin (HbA1c), triglycerides, LDL cholesterol, serum and urinary creatinine, uric acid, aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT), lactate, and complete blood count. The following glucometric parameters recorded during the 14 days preceding the study visit will be collected through continuous glucose monitoring (CGM) systems and downloaded from dedicated platforms: * Glucose Management Indicator (GMI); * coefficient of variation (CV%); * Time in Range (TIR: glucose ≥70 and ≤140 mg/dL); * Time Above Range (TAR: level 1 hyperglycemia \>140 and ≤180 mg/dL; level 2 hyperglycemia \>180 mg/dL); * Time Below Range (TBR: level 1 hypoglycemia ≥54 and \<70 mg/dL; level 2 hypoglycemia \<54 mg/dL); * number of hypoglycemic events. Dietary intake of calories, macronutrients, and micronutrients will be assessed through a 7-day food diary. Participants will complete the food diary according to routine clinical practice, as patients with glycogen storage disease regularly use food diaries during nutritional follow-up. To ensure the quality and consistency of the collected data, participants will receive standardized training from a dietitian prior to diary completion. Instructions will include meal timing, food description, portion size estimation, dose and timing of raw cornstarch administration, and accurate recording of meal initiation and completion times. Following completion, food diaries will be reviewed and harmonized by the same dietitian involved in routine nutritional follow-up. This process will include verification of diary completeness, correction of omissions or inconsistencies through direct patient clarification, and conversion of reported quantities into standardized units (grams, milliliters, equivalent portions). Dietary data will be entered into the Metadieta software database, based on CREA Food Composition Tables. For each food item, the software automatically calculates energy intake, macronutrients (carbohydrates, proteins, lipids), and micronutrients (vitamins and minerals). The software also allows automated calculation of average daily nutrient and caloric intake for both quantitative and qualitative dietary analyses. Meals extracted from the food diaries will be categorized as "meals with cornstarch" in patients routinely consuming raw cornstarch during main meals according to medical prescription, and "meals without cornstarch" in patients not routinely consuming cornstarch during main meals. To evaluate the effect of meals consumed with or without concomitant raw cornstarch supplementation on postprandial glycemic response, the following dynamic glycemic indices will be considered: * glucose peak (maximum postprandial glucose value); * glucose nadir (minimum glucose value following the peak); * time to peak (minutes from meal initiation to maximum glucose value); * time to nadir (minutes from peak to minimum glucose value); * glucose rise and decline rates (mg/dL/min); * incremental area under the curve (iAUC), calculated using the trapezoidal method, considering the glucose value at meal initiation as baseline. Postprandial glycemic response will be evaluated at 5-minute intervals, both as glucose profiles and as incremental area under the curve (iAUC). The iAUC will be used to assess total, early, and late postprandial glycemic responses. The glucose value corresponding to meal initiation will be considered time 0, and subsequent glucose measurements will be analyzed for up to 4 hours. Biological sample collection will include:blood samples: one EDTA tube and one serum tube (total blood volume: 5 mL);urine sample: one 12 mL collection tube. Biological sample collection is part of routine clinical follow-up procedures for patients with hepatic glycogen storage disease. Residual biological samples collected during the study, appropriately processed and aliquoted, will be stored at -80°C at the Complex Operative Unit of Diabetology for a maximum period of 7 years after study completion, after which they will be destroyed. Samples will not be transferred to third parties unrelated to the study and will not be used for purposes other than those specified without obtaining additional participant consent. Statistical analysis: Continuous variables will be expressed as mean ± standard deviation (SD), whereas categorical variables will be expressed as percentages (%). Comparisons of continuous variables between groups will be performed using independent-sample t-tests. Postprandial glycemic responses will be analyzed using repeated-measures general linear models to compare meals consumed by patients routinely taking raw cornstarch during main meals with meals consumed by patients not taking cornstarch during meals. Specific glycemic indices (iAUC, glucose peak, glucose nadir, time to peak, time to nadir, and the difference between time to peak and time to nadir) will also be compared between groups using independent-sample t-tests. CGM-derived metrics and glucose profile will be adjusted for potential confounding factors using linear mixed-effects models, including age, sex, body mass index (BMI), and menstrual cycle phase (when applicable) as covariates. Differences with p \< 0.05 will be considered statistically significant. All statistical analyses will be performed using SPSS version 30.0 (SPSS, Chicago, IL, USA) or later versions. Sample size estimation: Glycogen Storage Disease type I has an estimated incidence of approximately 1:100,000 live births. Approximately 20 adult patients with hepatic glycogenosis are currently followed at the Complex Operative Unit of Diabetology of the University Hospital "Federico II", of whom 15 routinely use CGM systems and meet the inclusion criteria. According to therapeutic indications, patients routinely consume raw cornstarch during the day, with some consuming it during meals and others between meals. Since no previous studies have evaluated postprandial glycemic variability assessed by CGM after meals with or without raw cornstarch supplementation in patients with GSD, the primary endpoint of the study is the difference in time to glucose nadir between the two groups. A difference in time to nadir of 20 ± 5 minutes is considered clinically significant. Sample size estimation, assuming a two-sided significance level of 0.05 and 80% statistical power, indicated a required sample size of 6 participants. Considering an expected dropout rate of 20%, the total planned enrollment has been set at 8 participants.