“We believe that our meta-analytic summary of published and unpublished data from eight randomized controlled trials using HbA1c thresholds, a first in the literature, will lead to more informed clinical decision making in the management of type 2 diabetes,” wrote the investigators.
Research has suggested that restricting dietary intake of carbohydrates, most of which is absorbed in the body as glucose or fructose, could improve blood glucose control and T2D outcomes.
However, this is the first systematic review to describe whether LCDs have an effect on the rate of diabetes remission. Additionally, no previous reviews have taken into consideration potential thresholds that help patients and physicians with interpreting the effects of therapy, the authors said.
To be included, trials had to investigate allocation to an LCD (<26% calories from carbohydrates or <130 g/day) for at least 12 weeks, with or without an exercise, lifestyle, or behavioral recommendations. The investigators searched through 4 trial databases, 3 trial registries, and 4 unpublished sources.
Out of 14,759 trials identified, 23 randomized control trials assessing the safety and efficacy of LCDs among patients with T2D fit the inclusion criteria, which accounted for 1357 patients. The trials predominately consisted of overweight and obese patients and 61% (n = 14) included patients being treated with insulin.
The sizes of the trials ranged from 12 to 144 patients, who had a mean age range of 47 to 67 years. Twelve (52%) of the trials met the criteria for very low carbohydrate diets (<10% daily calories from carbohydrates or <50 g/d). Patients on low fat diets were mainly used as controls (78%, n = 18). Treatment periods lasted between 3 months and 2 years. The risk of bias was determined to be low in 40.6% of trials.
Eight studies yielded reports on diabetes remission at 6 months. When remission was defined by an HbA1c level below 6.5% independent of medication use, LCDs increased the chances of remissions by an additional 32 per 100 patients studied (risk difference, 0.32; 95% CI, 0.17-0.47).
When the definition of remission was an HbA1c level below 6.5% without receiving diabetes medications, remission was affected by LCDs at a lower rate (risk difference, 0.05; 95% CI, -.05-0.14).
Remission was reported after 12 months in 3 studies. When remission was defined independently of medication use, remission increased with LCDs (risk difference, 0.10; 95% CI, -0.02-0.21). The rate of remission was lower when the definition included absence of medications (risk difference, -.04; 95% CI, -0.16-0.09).
Additionally, the investigators observed clinically significant weight loss, reduced medication use, improved triglycerides concentrations, and enhanced insulin sensitivity at 6 months. However, these benefits were diminished at 12 months, which was in line with previous reviews.
The investigators identified several limitations, including that there is no standard definition of diabetes remission, there are safety concerns surrounding LCDs, and that the results may have been confounded by restriction of caloric intake.
“Considering this and a recent systematic review of cohort studies suggesting that long term LCDs are associated with increased mortality, clinicians might consider short term LCDs for management of type 2 diabetes, while actively monitoring and adjusting diabetes medication as needed,” wrote the investigators.
Goldenberg JZ, Day A, Brinkworth GD, et al. Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: Systematic review and meta-analysis of published and unpublished randomized trial data. BMJ. Published online January 13, 2021. doi: 10.1136/bmj.m4743