Chrono Nutrition and Insulin Resistance in Diabetes

Study Overview
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Brief Summary
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The goal of this randomized clinical trial is to determine the effect of a chrono nutrition intervention compared with a usual dietary intervention on insulin resistance in individuals with type 2 diabetes with overweight or obesity over a 6-month period. The main question it aims to answer is: What is the effect of a chrono nutrition intervention compared to a standard intervention on insulin resistance in individuals with T2D (type 2 diabetes) with overweight or obesity over a 6-month period? Participants: Will be asked to fast for 12 hours each day. During the fasting period, they may consume non-caloric beverages such as plain water, coffee, or unsweetened tea. They will be asked to follow a dietary plan in which the total daily calorie intake will be calculated using indirect calorimetry, subtracting 500 calories from the total calorie amount. The dietary plan will have the following macronutrient distribution: 40% carbohydrates (<10% simple carbohydrates), 20% protein, and 40% fats (6-11% polyunsaturated, 15-20% monounsaturated, and <10% saturated). The plan will consist of 3 meals: breakfast will account for 40% of the total calories. Dinner will include only 10% of the total grams of carbohydrates. The order of food consumption should be: 1) vegetables, 2) proteins, 3) complex carbohydrates, and 4) simple carbohydrates (fruits). Researchers will compare the chrono nutrition strategy with a standard dietary intervention to see the effect in insulin resistance.

Detailed Description
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Type 2 diabetes (T2D) is considered one of the main public health problems. During the last decade the incidence of T2D has increased exponentially leading to an increased incidence in cardiovascular disease, premature death, blindness and non-traumatic limb amputation. Novel therapeutic interventions have become imperative. Dietary interventions are the cornerstone in managing and preventing T2D, however there is heterogeneity in the interventions and approaches currently available. The main objective of a dietary intervention is modest weight reduction achieved through calorie deficit and reduction in the consumption of carbohydrates and fats. Dietary interventions with a chrono nutrition focus establish an eating regime with calorie and macronutrient distribution taking into account sleeping and fasting hours, which are associated with metabolic alterations. This approach looks beyond calorie deficit and weight loss as primary outcomes. Nutrition, physical activity, and education are fundamental pillars for achieving metabolic control in T2D. It is well-described that a nutritional treatment alone can improve glycemic control and the quality of life of patients. It is interesting to note that the timing of meals throughout the 24-hour period seems to play an important role, similar to the number of meals per day or the total calorie intake. Furthermore, the daily pattern of fasting-feeding is influenced by the sleep-wake cycle pattern, which is one of the most evident adaptations to circadian rhythms and plays a significant role in maintaining optimal health. Interventions targeting aspects such as food type, meal timing, quality, and quantity can be a simple and promising strategy that can positively or negatively impact metabolic health, regardless of body weight modification. This evidence supports chrono nutrition as a novel strategy in the field of nutrition, primarily focusing on studying the interaction between nutrition, feeding, and the circadian rhythm. The implementation of new nutritional strategies based on circadian rhythms contributes to improving adherence to dietary treatment and preventing potential complications.

Official Title
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Effect of a Chrono Nutrition Intervention on Insulin Resistance in Adults With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Other: Chrono nutrition
* Other: Standard


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with type 2 diabetes (T2D) HbA1c < 8.5% BMI ≥ 25 kg/m2 and < 35 kg/m2 Stable pharmacological treatment for the last 3 months Willingness to participate in the protocol. Exclusion Criteria: Insulin treatment Hospitalization in the previous three months Disease with adverse prognosis (SIDA, cancer) Rheumatologic diseases under immunosuppressive treatment (SLE, RA) Acute infection or febrile syndrome Hepatic cirrhosis Glomerular filtration rate <60 ml/min Other diabetes types (LADA, T1, MODY) Fasting triglycerides >500 mg/dl Pregnancy Lactation Steroid treatment High performance athletes Estrogen treatment Weight reduction >5% in the last three months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Chrono nutrition intervention: Participants will be asked to fast for 12 hours each day. During the fasting period, they may consume non-caloric beverages such as plain water, coffee or unsweetened tea. They will be asked to follow a dietary plan in which the total daily calorie intake will be calculated using indirect calorimetry, subtracting 500 calories from the total calorie amount. The dietary plan will have the following macronutrient distribution: 40% carbohydrates (<10% simple carbohydrates), 20% protein, and 40% fats (6-11% polyunsaturated, 15-20% monounsaturated, and <10% saturated). The plan will consist of 3 meals: breakfast will account for 40% of the total calories. Dinner will include only 10% of the total grams of carbohydrates. The order of food consumption should be: 1) vegetables, 2) proteins, 3) complex carbohydrates, and 4) simple carbohydrates (fruits).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chrono nutrition<br>During the 6-month period, participants will be asked to fast for 12 hours each day. During the fasting period, they may consume non-caloric beverages such as plain water, coffee, or unsweetened tea. The total daily calorie intake will be calculated using indirect calorimetry, considering the participant's current weight, age, sex, and physical activity level. 500 calories will be subtracted from the total calorie amount. The dietary plan will have the following macronutrient distribution: 40% carbohydrates (<10% simple carbohydrates), 20% protein, and 40% fats (6-11% polyunsaturated, 15-20% monounsaturated, and <10% saturated). The plan will consist of 3 meals and breakfast will account for 40% of the total calories. During dinner, only 10% of the total grams of carbohydrates will be included. The order of food consumption should be as follows: 1) vegetables, 2) proteins, 3) complex carbohydrates, and 4) simple carbohydrates (fruits). | Other: Chrono nutrition<br>* An integral nutritional strategy involving timing, order and distribution of macronutrients<br>|
| Active Comparator: Standard<br>The total daily calorie intake will be calculated using indirect calorimetry, considering the participant's current weight, age, sex, and physical activity level. 500 calories will be subtracted from the total calorie amount. The dietary plan will have the following macronutrient distribution: 40% carbohydrates (<10% simple carbohydrates), 20% protein, and 40% fats (6-11% polyunsaturated, 15-20% monounsaturated, and <10% saturated). The plan will consist of 3 meals with an isocaloric distribution, with each meal containing 33% of the total calories. | Other: Standard<br>* Conventional nutritional strategy involving isocaloric distribution with no specific timing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin resistance (M value) | Change in insulin resistance (M value) assessed with an euglycemic-hyperinsulinemic clamp. | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in visceral adipose (liters) | Change in visceral adipose tissue amount | Six months | 
| Change in glycated hemoglobin (%) | Change in glycated hemoglobin | Six months | 
| Change in lipid profile (mg/dl) | Change in lipid profile | Six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus, Chrono nutrition, Insulin resistance