Vey Low-Energy Ketogenic Therapy in Adults With Type 1 Diabetes and Obesity on Intensive Insulin Therapy Using Advanded Hybrid Closed Loop System

Overview

Overweight and obesity are frequent in adults with type 1 diabetes (T1D), with prevalence exceeding 50% in recent studies. Excess weight in T1D is associated with higher cardiometabolic risk and therapeutic challenges, while effective and safe weight management strategies are still limited. This single-center, single-arm feasibility study will evaluate the efficacy and safety of a Very Low-Energy Ketogenic Therapy (VLEKT; 600-800 kcal/day) in adults with T1D and obesity treated with Advanced Hybrid Closed Loop (AHCL) insulin delivery systems. Participants will follow a structured 4-week program with commercial very-low-carbohydrate, high-protein meal replacements, under close medical supervision. The primary endpoint is change in body weight at 4 weeks. Secondary outcomes include body composition, muscle strength, glucose metrics, insulin requirements, biochemical parameters, and patient-reported outcomes. Safety will be assessed through hypoglycemia incidence, ketone monitoring, and occurrence of diabetic ketoacidosis (DKA). The study will enroll 14 participants. It is expected that VLEKT will achieve \~5% weight loss within one month while maintaining glycemic safety under AHCL technology.

Excess weight in type 1 diabetes (T1D) is increasingly recognized as a critical clinical problem. Factors contributing to weight gain include intensive insulin therapy, compensatory intake of high-energy foods to prevent hypoglycemia, reduced physical activity due to fear of hypoglycemia, and pathophysiological mechanisms such as adipose tissue dysfunction and insulin resistance. Current therapeutic options for weight management in T1D are limited compared with type 2 diabetes, and novel approaches are urgently needed. Ketogenic and very low-carbohydrate diets are effective in obesity and type 2 diabetes but have traditionally been discouraged in T1D because of risks of hypoglycemia, dyslipidemia, poor adherence, and diabetic ketoacidosis (DKA). The introduction of Advanced Hybrid Closed Loop (AHCL) systems, which combine continuous glucose monitoring with automated insulin delivery, provides a safer framework to test structured dietary interventions that were previously considered unsuitable in this population. This feasibility study investigates a Very Low-Energy Ketogenic Therapy (VLEKT) for 4 weeks in adults with T1D and obesity using AHCL technology. The intervention will consist of commercially available meal replacements (600-800 kcal/day, \<30 g/day carbohydrates, adequate protein supply) with strict monitoring of capillary ketones and insulin adjustments. Baseline assessments include anthropometry, bioimpedance-derived body composition, handgrip strength, biochemical testing, continuous glucose monitoring metrics, and validated questionnaires (SF-12, IPAQ, PSQI, FH-15). Participants will attend weekly visits for clinical review, adherence reinforcement, safety checks, and repeat assessments. At study completion, a gradual reintroduction of conventional meals will be initiated. The primary endpoint is absolute weight change after 4 weeks. Secondary endpoints include proportion achieving ≥5% weight loss, changes in body composition and muscle strength, glucose control (TIR, TAR, TBR, CV, GMI, GRI, TITR), insulin requirements, lipid and liver function markers, and patient-reported outcomes. Safety evaluation will focus on hypoglycemia incidence and DKA events. Sample size calculation determined that 14 participants are required to detect a clinically relevant mean weight reduction of \~5%. The results will provide initial evidence on the feasibility, metabolic impact, and safety of VLEKT in this specific population, laying the groundwork for larger randomized controlled trials.