Does restricting carbohydrate intake to earlier in the day improve glycemic control? Original paper

In this randomized controlled trial, restricting carbohydrate intake to breakfast and lunch, compared to consuming carbohydrates at each of the 3 main meals, did not improve glycemic control in people with type 2 diabetes.

This Study Summary was published on February 5, 2024.

Quick Summary

In this randomized controlled trial, restricting carbohydrate intake to breakfast and lunch, compared to consuming carbohydrates at each of the 3 main meals, did not improve glycemic control in people with type 2 diabetes.

What was studied?

The effects of early time-restricted carbohydrate consumption (eTRC) in people with type 2 diabetes (T2D).

The primary outcome was the change in HbA1c. The secondary outcomes included anthropometrics, fatty liver index, glucose tolerance, measures of glycemic variability (e.g., average glucose, time spent in hyperglycemia), fasting glucose and insulin, free fatty acids, glucagon-like peptide 1, beta-cell function, liver enzymes, blood pressure, heart rate, and blood lipids.

Who was studied?

23 participants with T2D (average age of 67; 52% men, 48% women; 100% non-Hispanic white).

How was it studied?

In this 12-week randomized controlled trial, the participants consumed a Mediterranean-style diet with or without eTRC. The diets were matched in multiple ways, including the following:

  • Energy restriction, calculated based on the individual’s energy requirement to achieve a weight loss of 5% of initial body weight
  • Macronutrient distribution (50% carbohydrate, 30% fat, and 20% protein)
  • Meal frequency (3 meals/day)

In the eTRC diet group, the participants were instructed to restrict their intake of carbohydrates to breakfast and lunch, while participants in the control group were instructed to consume carbohydrates at each meal.

The participants met with a registered dietitian every 4 weeks to evaluate changes in body composition, diet adherence (assessed using 3-day food diaries), and glycemic variability (measured over 14 days using continuous glucose monitors). Glucose tolerance was assessed at baseline and the end of the study using a mixed meal test consisting of 37 grams of carbohydrate, 12 grams of fat, and 12 grams of protein. The data obtained from this test was used to calculate beta-cell function.

What were the results?

Changes in the examined outcomes (most of which improved in both groups) did not differ between groups.

Compared to the control group, participants in the eTRC group reported consuming a lower proportion of carbohydrates with their evening meal (8.8% vs. 28.1%).

The big picture

The main idea behind eTRC is to align carbohydrate consumption with the body’s circadian rhythms. Circadian rhythms are periodic patterns in physiology, metabolism, and behavior that repeat themselves roughly every 24 hours. Metabolic processes all follow a rhythm across the day, meaning that there are ebbs and flows, or distinct periods when they are upregulated and downregulated. Evidence suggests glucose metabolism peaks in the morning. Several studies have reported that blood glucose levels are lower (better) following the consumption of carbohydrates in the morning, compared to the late afternoon or evening,[1][2] which seems to be a product of beta-cell function and insulin sensitivity being better earlier in the day.[1][2]

A strength of the summarized study is that it matched total daily energy intake, macronutrient distribution, and diet quality between groups. Thus, any differences in the examined outcomes between groups would presumably be due to differences in the distribution of carbohydrate intake, as opposed to the results being influenced by confounders, such as one group consuming less total energy, more protein, and/or more fiber and fruits and vegetables than the other.

Indeed, it was reported that, compared to the control group, the eTRC group consumed 58% more carbohydrates at breakfast, similar amounts at lunch, and 69% less at dinner (approximately 16 vs. 47 grams of carbohydrate). Although the difference in carbohydrate intake at dinner was seemingly small when considering the total amounts consumed, this difference was sufficient to induce disparate daily glucose profiles. As shown by the figure below, there were only 2 postprandial (postmeal) glucose elevations in the eTRC group, whereas there were 3 in the control group, demonstrating the effect of minimal carbohydrate intake at dinner in the eTRC group.

14-day continuous glucose monitoring reports

image

Despite differences in the distribution of carbohydrate intake and daily glucose profiles, changes in measures of glycemic control and insulin sensitivity did not differ between groups. There are a couple of potential reasons for this, which are worth highlighting because they are pivotal to understanding how the summarized study fits within the body of evidence at large.

For starters, it cannot be said for certain that the results are generalizable to a eucaloric diet. In accordance with the diets being designed to induce a weight loss of 5% of initial body weight by the end of the study, there was significant weight loss in both groups, with no difference between groups. It’s possible that the metabolic benefits of caloric restriction are so potent that they overwhelmed the potential benefits of consuming the vast majority of carbohydrates earlier in the day.[3][4]

A similar claim could be made for the Mediterranean-style diet intervention, as there is evidence to suggest that such an intervention can improve a variety of cardiometabolic risk factors, including insulin sensitivity, even without weight loss.[5] In both groups, the prescribed diet was designed to be rich in whole-grain cereals, fruits, vegetables, nuts and seeds, legumes, fish, eggs, poultry, and olive oil, and low in red and processed meat, sugar, salt, saturated fat, and alcohol.

Considering these two factors, it’s possible that if the participants consumed their usual diets, and the groups only differed in the distribution of carbohydrate intake, differences between groups would have been observed.

In support of this hypothesis, a 5-week crossover study had participants with prediabetes consume the same eucaloric diet, but with one condition requiring that participants consume all of their meals by 3 p.m. (eTRE, 6-hour eating window). This trial reported that eTRE improved insulin sensitivity and beta-cell function, compared to eating over a 12-hour eating window.[6] In agreement, a meta-analysis of randomized controlled trials concluded that compared to later time-restricted eating (typically an eating window of 12 p.m. to 8 p.m.), early time-restricted eating (the last meal of the day is eaten before 4 p.m.) was better for improving insulin sensitivity.[7]

Similar results have been reported in studies that did not incorporate an extended fasting period. A 4-week crossover study had participants consume energy-matched and macronutrient-matched diets, with the only notable difference between conditions being the distribution of carbohydrate-rich and fat-rich meals.[8] In the HF/HC condition, participants ate fat-rich meals until 1:30 p.m. and carbohydrate-rich meals between 4:30 and 10 p.m., while in the HC/HF condition, participants ate carbohydrate-rich meals until 1:30 p.m. and fat-rich meals between 4:30 and 10 p.m. At the end of each intervention, the participants consumed a fat-rich and a carbohydrate-rich meal in a laboratory — the order of which depended on the participant’s assigned dietary intervention — and postprandial glucose levels were measured for 3 hours after each meal. It was found that, in participants with impaired fasting glucose or impaired glucose tolerance, HF/HC increased the overall glucose level over 6 hours by about 8%, compared to HC/HF.

In a separate crossover study, participants with T2D consumed energy-matched and macronutrient-matched diets that differed in whether the most calorically dense meal was consumed for breakfast (Bdiet) or dinner (Ddiet). They consumed each diet for 7 days, and on day 7, the diets were consumed in a laboratory so the researchers could measure the blood glucose response to each meal. It was found that the Bdiet decreased the whole-day glucose level by 20%, compared to the Ddiet.[9]

In contrast to these findings, and similar to the summarized study, a study that had men with obesity and insulin resistance consume 1 of 2 hypocaloric diets that differed in whether 50% of daily energy intake was consumed at breakfast or dinner, reported that changes in insulin sensitivity did not differ between groups.[10] Notably, the average weight loss was a little over 6% of initial body weight in both groups, suggesting that in the context of significant weight loss, energy distribution does not meaningfully affect changes in insulin sensitivity.

Collectively, the results of the aforementioned studies suggest that, in the context of a roughly eucaloric (body weight-maintaining) diet, consuming the majority of calorie/carbohydrate intake in the first half of the day has a small beneficial effect on glycemic control and insulin sensitivity, compared to consuming the majority of calorie/carbohydrate intake in the second half of the day. However, these potential benefits are grossly outweighed by the benefits of caloric restriction. Meanwhile, in the context of a hypocaloric diet that induces significant weight loss, the distribution of energy and carbohydrate intake seems to have little-to-no effect on glycemic control and insulin sensitivity.

This Study Summary was published on February 5, 2024.

References

  1. ^Poggiogalle E, Jamshed H, Peterson CMCircadian regulation of glucose, lipid, and energy metabolism in humansMetabolism.(2018 Jul)
  2. ^Daniela Jakubowicz, Julio Wainstein, Shani Tsameret, Zohar LandauRole of High Energy Breakfast "Big Breakfast Diet" in Clock Gene Regulation of Postprandial Hyperglycemia and Weight Loss in Type 2 DiabetesNutrients.(2021 May 5)
  3. ^Andreea Soare, Edward P Weiss, Paolo PozzilliBenefits of caloric restriction for cardiometabolic health, including type 2 diabetes mellitus riskDiabetes Metab Res Rev.(2014 Mar)
  4. ^Faidon Magkos, Gemma Fraterrigo, Jun Yoshino, Courtney Luecking, Kyleigh Kirbach, Shannon C Kelly, Lisa de Las Fuentes, Songbing He, Adewole L Okunade, Bruce W Patterson, Samuel KleinEffects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with ObesityCell Metab.(2016 Apr 12)
  5. ^Marno C Ryan, Catherine Itsiopoulos, Tania Thodis, Glenn Ward, Nicholas Trost, Sophie Hofferberth, Kerin O'Dea, Paul V Desmond, Nathan A Johnson, Andrew M WilsonThe Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver diseaseJ Hepatol.(2013 Jul)
  6. ^Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CMEarly Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with PrediabetesCell Metab.(2018 Jun 5)
  7. ^Liu J, Yi P, Liu FThe Effect of Early Time-Restricted Eating vs. Later Time-Restricted Eating on Weight Loss and Metabolic Health: A Network Meta-Analysis of Randomized Controlled Trials.J Clin Endocrinol Metab.(2023-Jan-26)
  8. ^Kessler K, Hornemann S, Petzke KJ, Kemper M, Kramer A, Pfeiffer AF, Pivovarova O, Rudovich NThe effect of diurnal distribution of carbohydrates and fat on glycaemic control in humans: a randomized controlled trial.Sci Rep.(2017-Mar-08)
  9. ^Jakubowicz D, Wainstein J, Ahrén B, Bar-Dayan Y, Landau Z, Rabinovitz HR, Froy OHigh-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: a randomised clinical trialDiabetologia.(2015 May)
  10. ^Versteeg RI, Ackermans MT, Nederveen AJ, Fliers E, Serlie MJ, la Fleur SEMeal timing effects on insulin sensitivity and intrahepatic triglycerides during weight loss.Int J Obes (Lond).(2018-Feb)