Chrono Nutrition and Insulin Resistance in Diabetes (Chrono)

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Other: Chrono nutrition; Other: Standard

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chrono nutrition; 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; An integral nutritional strategy involving timing, order and distribution of macronutrients
Active Comparator: Standard; 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; Conventional nutritional strategy involving isocaloric distribution with no specific timing

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hepatic steatosis and fibrosis (decibels and kilopascals)	Change in hepatic steatosis and fibrosis assessed with elastography	Six months
Hunger and satiety (score)	Change in hunger and satiety assessed with visual analog scale for hunger and satiety	Six months

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

General Publications

• Farshchi HR, Taylor MA, Macdonald IA. Beneficial metabolic effects of regular meal frequency on dietary thermogenesis, insulin sensitivity, and fasting lipid profiles in healthy obese women. Am J Clin Nutr. 2005 Jan;81(1):16-24. doi: 10.1093/ajcn/81.1.16.
• Stote KS, Baer DJ, Spears K, Paul DR, Harris GK, Rumpler WV, Strycula P, Najjar SS, Ferrucci L, Ingram DK, Longo DL, Mattson MP. A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults. Am J Clin Nutr. 2007 Apr;85(4):981-8. doi: 10.1093/ajcn/85.4.981.
• Henry CJ, Kaur B, Quek RYC. Chrononutrition in the management of diabetes. Nutr Diabetes. 2020 Feb 19;10(1):6. doi: 10.1038/s41387-020-0109-6.
• Lopez-Minguez J, Saxena R, Bandin C, Scheer FA, Garaulet M. Late dinner impairs glucose tolerance in MTNR1B risk allele carriers: A randomized, cross-over study. Clin Nutr. 2018 Aug;37(4):1133-1140. doi: 10.1016/j.clnu.2017.04.003. Epub 2017 Apr 10.
• Jakubowicz D, Wainstein J, Landau Z, Ahren B, Barnea M, Bar-Dayan Y, Froy O. High-energy breakfast based on whey protein reduces body weight, postprandial glycemia and HbA1C in Type 2 diabetes. J Nutr Biochem. 2017 Nov;49:1-7. doi: 10.1016/j.jnutbio.2017.07.005. Epub 2017 Jul 21.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: October 5, 2023
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Insulin resistance; Diabetes mellitus; Chrono nutrition
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: 4494

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No