Comparative Study of the Postprandial Glycemic Profile After Consumption of a High-fat Meal (Pizza) Between the Open-loop System (Medtronic MiniMed 640G) and the Hybrid Closed-loop System (Medtronic MiniMed 780G) in Patients With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion Pumps.

Overview

The aim of this interventional clinical study is to compare the postprandial glycemic profile of patients with type 1 diabetes using either an open-loop (Medtronic Minimed 640G) or closed-loop (Medtronic Minimed 780G) insulin pump, after consuming a high-fat meal (pizza). The new advanced Medtronic MiniMed 780G insulin pump (closed hybrid loop) features an advanced algorithm that enables the automatic administration of corrective microdoses of insulin (microboluses) every 5 minutes. The open-loop pump offers the option of a dual-wave bolus pattern for insulin delivery, which is currently considered the best approach for managing such high-fat meals, a feature that is not available in the closed-loop pump. The main questions to answer are: 1. To what extent can the new closed-loop insulin pump with automatic corrective microdoses of insulin manage the late postprandial hyperglycemia caused by a high-fat meal like pizza, which is extremely difficult for type 1 diabetes patients to manage? 2. To what extent should protein and fat, in addition to carbohydrates, be accounted for in patients with type 1 diabetes using the closed-loop pump when consuming high-fat meals like pizza? Participants will be adults (\> 18years old) with type 1 diabetes using the MiniMed 780G pump (with either aspart or lispro insulin) and who are regularly followed up at the Insulin Pump Outpatient Department of the Diabetes Center of the Laiko General Hospital, National and Kapodistrian University of Athens Medical School, in Athens, Greece. They will undergo three study visits. During these visits, different strategies for managing a high-fat meal will be compared using both the closed-loop and open-loop modes of the insulin pump. A brief clinical history will be taken (duration of diabetes, conditions at initial diagnosis, treatment regimen, complications), and anthropometric measurements (height, weight, waist circumference) will be recorded. Data from the insulin pumps will be uploaded to a computer to document the pump's basic settings (insulin-to-carbohydrate ratio, insulin sensitivity factor, hourly basal rates, glucose target, active insulin time), and the most recent HbA1c value will be noted. The meal test will start only if the sensor glucose level upon arrival is below 180 mg/dL. An intravenous catheter will be placed in a forearm vein for repeated blood sampling to measure venous glucose levels at time 0 (pre-meal), 30, 60, 90, 120, 150, 180, 210, and 240 minutes after consuming the meal. At the same times, capillary blood glucose will also be measured, the glucose sensor readings from the pump will be recorded as well. The meal test will then begin, using different meal coverage approaches to be compared.

Participants will consume a total of 250 g of pizza, (a "four cheese" type pizza with classic crust) with the following macronutrient composition by percentage: 37.9% fat, 41.07% carbohydrates and dietary fiber, and 21.01% protein, and it must be consumed within 10 minutes, with or without water. One tablespoon of olive oil will be added to the above meal to increase its fat content. After the addition of olive oil, the final meal composition in macronutrients will be as follows: 41.25 g fat (48.62% \& 366.25 kcal), 64 g carbohydrates (33.98% \& 256 kcal) and 32.75 g protein (17.39% \& 131 kcal. During the three different study visits, three different meal consumption management approaches will be applied. Given the ability of the 780G insulin pump to operate as a 640G pump, this enables a direct comparison of different fat-rich meal management approaches in the same patients using only one type of pump. In the first study visit, involving dual-wave insulin bolus in open-loop conditions, patients will exit the automatic mode of the 780G pump immediately prior to the meal test and enter open-loop mode using the pump as a 640G. The carbohydrate content of the meal (64 g) will be declared, and the meal insulin dose will be increased by 30% for fat and 20% for protein, a total increase of 50%. The dual-wave bolus pattern of insulin delivery will be used: 50% of the recommended dose will be given 10 minutes before the meal, and the remaining 50% will be delivered as an extended bolus over the next 4 hours. In the second study visit, involving a single insulin bolus in closed-loop conditions, only the carbohydrate grams of the meal will be declared (as fat and protein are not recommended to be included in the bolus calculation with the 780G pump). The pump will deliver a single bolus of insulin 10 minutes before the meal. In the third visit, participants will receive the same predetermined amount of pizza in closed-loop conditions. Ten minutes before the meal, 64 g of carbohydrates will be declared, and 1 hour after the meal has started, the insulin dose will be increased by 30% for fat and 20% for protein, a total of 50%, calculated based on 50% of the carbohydrate grams declared before the meal. The total and cumulative areas under the curve (AUC), reflecting postprandial glycemic levels for up to 4 hours post-meal, will be calculated and compared across the three approaches using non-inferiority statistical analysis. Additionally, sensor glucose data (measured every 5 minutes) will be collected for a total of up to 8 hours post-meal, to capture any differences in late postprandial hyperglycemic peaks. All participants will receive detailed verbal and written information about the study procedures and objectives and will sign an informed consent form.