PREdiabetes GLycemic Impact and Data Evaluation

Prediabetes is considered a critical stage at which effective prevention of the development of diabetes is possible, provided that early detection and adequate glycemic control. International clinical guidelines and multicenter studies suggest that early intensive glycemic control is associated with a better prognosis and a reduced risk of complications. However, standard self-monitoring has limited information on glycemic variability, which is especially important in the early stages of carbohydrate metabolism disorders, including prediabetes. Routine indicators such as fasting blood glucose, 1 and 2 hours after a meal, and glycated hemoglobin (HbA1c) do not always clearly differentiate between diabetes, prediabetes, and normal carbohydrate metabolism. Recently, there has been a need for more comprehensive blood glucose monitoring strategies that cover the entire spectrum of glycemic variability. Continuous glucose monitoring (CGMs) technology provides real-time glucose concentration data, overcoming the limitations of traditional monitoring methods. Recently, not only among people with diabetes, but also among people with prediabetes, there has been an increasing trend towards using CGM as a personal device to monitor glucose levels and promote healthy habits such as increased activity, diet, and sleep. Their motivation is to improve their own glycemic control and avoid the future development of diabetes and its associated complications, to optimize blood glucose levels to achieve peak mental or physical performance, and to use personal monitoring data to develop sustainable behavioral skills. The contactless 24-hour monitoring system is considered a promising tool for personalized glycemic control, but its use in people with prediabetes has not been studied enough This is a prospective, open-label, randomized controlled trial involving 80 adult patients with prediabetes recruited at the Bogomolets National Medical University. Participants were randomized in a 1:1 ratio to either the Real-Time Continuous Glucose Monitoring (CGM group) or the control group (standard Self-Monitoring of Blood Glucose \[SMBG\] using conventional glucometers). Participants will undergo a 3-month observation period. The use of the assigned monitoring devices (CGM or SMBG glucometer) and pedometers will last for the first 1 month. The study consists of three visits: Visit 1 (baseline), Visit 2 (1 month, end of intervention), and Visit 3 (3 months, follow-up period). During these visits, researchers will collect data on glycated hemoglobin (HbA1c), fructosamine, Cpeptide, HOMA-IR index, lipid profile, anthropometric indicators (body mass index (BMI), waist circumference), bioimpedance measurement, physical activity monitoring using pedometers, and SF-36 questionnaire to assess quality of life.

The gathered data will help determine whether continuous monitoring provided by CGM systems improves glycemic control and increases patient adherence to lifestyle changes compared to conventional SMBG methods.

• CGM Sibionics (Device): A registered medical device for real-time monitoring of glucose levels in interstitial fluid.
• On-Call Extra Glucometer (Device): Capillary glucose monitoring using fingerstick glucometer as per standard care.

Primary outcomes

• Changes in HbA1c level [at 3 month (end of follow-up period)]: HbA1c in %
• Changes in Fructosamine level [at 3 month (end of intervention period)]: Fructosamine in μmol/L

Secondary outcomes

• Homeostatic Model Assessment of Insulin Resistance (HOMA2-IR) [at 3 month (follow-up period) compared to baseline]: HOMA2-IR will be calculated based on fasting plasma glucose and fasting serum insulin levels using the non-linear Homeostasis Model Assessment. The score is continuous, theoretically starting from 0, where higher values indicate greater insulin resistance (a worse clinical outcome).
• insulin sensitivity (%S) [at 3 month (follow-up period) compared to baseline]: This model can be calculated using the software supplied by the Oxford Centre for Diabetes Endocrinology and Metabolism
• β-cell function (%B) [at 3 month (follow-up period) compared to baseline]: This model can be calculated using the software supplied by the Oxford Centre for Diabetes Endocrinology and Metabolism
• body mass index (BMI) [at 1 month (end of intervention) and 3 month (follow-up period) compared to baseline]: weight in kg and height in meters will be combined to report BMI in kg/m\^2
• waist circumferences (WC) [at 1 month (end of intervention) and 3 month (follow-up period) compared to baseline]: WC in cm
• visceral fat content [at 1 month (end of intervention) and 3 month (follow-up period) compared to baseline]: visceral fat content using electronic scales-analyzers of body composition Huawei (Smart Scale series 3/3 Pro
• Total Cholesterol (TC) [at 3 month (follow-up period) compared to baseline]: TC in mmol/l
• Tryglicerides (TG) [at 3 month (follow-up period) compared to baseline]: TG in mmol/l
• LDL-Cholesterol (LDL-C) [at 3 month (follow-up period) compared to baseline]]: LDL-C in mmol/l
• Physical activity levels [at 1 month (end of intervention) and 3 month (follow-up period) compared to baseline]: Daily number of steps as measured by a sealed pedometer
• Quality of Life Evaluation: Medical Outcomes Study Short-Form 36 (SF-36) [at 1 month (end of intervention) and 3 month (follow-up period) compared to baseline]: Health-related quality of life will be evaluated using the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire. The SF-36 consists of 36 items measuring 8 health domains, which are aggregated into two summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). For each domain and summary score, values are transformed to a scale ranging from a minimum of 0 to a maximum of 100. Higher scores represent better health status and a better quality of life outcome.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age of 18 years and older.
* Presence of prediabetes diagnosed according to criteria of the American Diabetes Association
* Persons who treated with diet and exercise alone or metformin on a stabilized dose for at least 3 months before the study;
* Ability to comply with protocol requirements and maintain a patient diary.
* Signed informed consent.

Exclusion Criteria:

* Presence of type 1 or type 2 diabetes;
* Decompensated liver or kidney diseases (GFR < 45 ml/min/1. 73 m²);
* Active cardiovascular diseases within 12 months of Visit 1, such as myocardial infarction, clinically significant arrhythmia, unstable angina, coronary artery bypass surgery, or angioplasty; or are expected to require coronary artery bypass surgery or angioplasty during the course of the study;
* Endocrine disorders (e.g., Itsenko-Cushing syndrome, acromegaly) that affect glycemia;
* Pregnancy or lactation;
* Mental or cognitive impairments that would interfere with study participation;
* Daily use of any form of steroid medication (oral, inhaled, injected) within the last 3 months;
* Recent use of any CGM within the last 12 months;
* Known allergy to sensor materials;
* Has evidence of current abuse of drugs or alcohol or a history of abuse that, in the investigator's opinion, would cause the individual to be noncompliant;
* Participation in another clinical study within the last 3 months.

• Nazarii Kobyliak, Principal investigator, Bogomolets National Medical University