饮食脂肪与月经周期阶段对1型糖尿病的影响 (DIABETEXX/3)

This clinical trial aims to evaluate how variations in dietary fat content and hormonal status influence postprandial glycemic response in individuals with type 1 diabetes (T1D), with a special focus on women. The main objective is to clarify the impact of both factors individually and their interaction, which could inform more personalized strategies for insulin adjustment, optimizing glycemic control, and improving patient outcomes.

The main objective is to investigate the effects of low-fat versus high-fat meals, sex, menstrual cycle phases, and their interaction on postprandial glycemic control in adults with T1D treated with advanced hybrid closed-loop (AHCL) insulin delivery systems.

Specifically, the study will:

• Compare postprandial glycemic responses after standardized low and high-fat meals in men and women with T1D.
• Assess the differences in postprandial glycemic responses between early follicular and late luteal phases in women, using standardized meals with low and high fat content.
• Identify sex-related differences in glycemic response after equivalent meals.

This research addresses the unmet clinical need for precise, tailored postprandial insulin dosing recommendations, especially among women whose insulin sensitivity fluctuates with menstrual phases. The results may contribute to sex-specific predictive models in AHCL systems, reducing acute complications and improving overall quality of life.

This is a randomized controlled crossover trial in which each participant serves as her/his own control. Fifty adults will be enrolled: 25 women and 25 men. Women will undergo four mixed-meal tests in random order:

• low-fat given during the early follicular phase,
• high-fat given during the early follicular phase,
• low-fat given during the late luteal phase,
• high-fat given during the late luteal phase. The menstrual phase will be confirmed with home-based hormonal monitoring devices that function with urine sample and use a single-use test wand (MIRA system).

Men will complete two mixed-meal tests (low-fat and high-fat), in randomized order.

All meals will be standardized for carbohydrate content and matched in other macronutrients, except for fat (with a 30-40g difference), administered after an 8-hour fast. The day of the mixed meal test, AHCL systems will be switched from automatic to manual mode just before eating to standardize the prandial insulin dose and to avoid differences in insulin infusion rates in the postprandial state due to algorithm compensations. Continuous glucose monitoring (CGM) and hourly capillary glucose testing will measure the postprandial response. Additional fasting blood samples will assess metabolic, hormonal, and lipid markers. Optional gastric emptying studies may be performed to exclude confounding gastroparesis in selected patients.

Participants will be recruited from the endocrinology outpatient unit of La Fe Polytechnic University Hospital . The projected recruitment period is from December 2025 to July 2027, with mixed-meal tests and data collection occurring between January 2026 and December 2027. Women are expected to complete the protocol in 6 weeks (4 tests), while men will require about 2 weeks (2 tests).

At baseline, participants will undergo blood tests to rule out endocrine disorders and confirm sex hormone status. Women participating in the study will use the MIRA home device to monitor their hormonal levels, allowing them to accurately determine and record the phases of their menstrual cycle as part of the study protocol. During meal tests, CGM (Freestyle Libre 3) will be used uniformly among subjects.

The study dependent variables will be the following:

• Postprandial glucose area under the curve - AUC_PG_5h
• Mean glucose level - MG
• Continuous glucose monitoring metrics - TIR, TAR, TBR
• Postprandial glucose standard deviation - SD
• Postprandial glucose coefficient of variation - CV
• Mean amplitude of glycemic excursions - MAGE
• Mean of daily differences (MODD)

Independent variables are

• Type of food: Meals with either low or high fat content.
• Sex and Hormonal status: men; women during the early follicular phase; women during the late luteal phase.

If successful, this study will inform the development of more sophisticated, individualized insulin dosing algorithms and AHCL system improvements, especially for women with T1D. Results may lead to more effective management strategies, reduced GV, lower incidence of complications, and increased quality of life. Insights may directly support the personalization of diabetes care and improve gender equity in treatment standards.