Low and very-low carb diets for type 2 diabetes remission – Systematic review

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Patients with type 2 diabetes who follow a strict low carbohydrate diet (LCD) for six months may temporarily experience greater rates of remission compared with other recommended diets without adverse effects, a meta-analysis found.

However, most of these benefits diminished at 12 months, a finding consistent with previous reviews, and some evidence showed worsening of quality of life and cholesterol levels at 12 months.

The researchers at Texas A&M University, National University of Natural Medicine-Portland, Juntendo University Graduate School of Medicine, Kitasato University, Skåne University Hospital-Malmö, University of Alberta-Edmonton, McMaster University, and St Joseph’s Healthcare, say doctors might consider short term strict low carbohydrate diets for managing type 2 diabetes, while actively monitoring and adjusting diabetes medication as needed.

Type 2 diabetes is the most common form of diabetes worldwide and diet is recognised as an essential part of treatment. But uncertainty remains about which diet to choose and previous studies have reported mixed results.

To address this evidence gap, a team of international researchers set out to assess the effectiveness and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes, compared with (mostly low fat) control diets.

Their findings are based on analysis of published and unpublished data from 23 randomised trials involving 1,357 participants.

LCDs were defined as less than 26% daily calories from carbohydrates and VLCDs were defined as less than 10% daily calories from carbohydrates for at least 12 weeks in adults (average age 47 to 67 years) with type 2 diabetes.

Outcomes were reported at six and 12 months and included remission of diabetes (reduced blood sugar levels with or without the use of diabetes medication), weight loss, adverse events and health related quality of life.

Although the trials were designed differently, and were of varying quality, the researchers were able to allow for this in their analysis.

Based on low to moderate certainty evidence, the researchers found that patients on LCDs achieved higher diabetes remission rates at six months compared with patients on control diets, without adverse events.

For example, based on moderate certainty evidence from 8 trials with 264 participants, those following a LCD experienced, on average, a 32% absolute risk reduction (28 fewer cases per 100 followed) in diabetes remission at 6 months.

LCDs also increased weight loss, reduced medication use, and improved body fat (triglyceride) concentrations at six months.

This study used robust methods to increase the precision and overall certainty of the effect estimates. But the authors acknowledge some limitations, such as the ongoing debate around what constitutes remission of diabetes, and uncertainty over the longer-term effectiveness and safety of LCDs.

They also stress that their results are based on moderate to low certainty evidence. As such, they suggest clinicians “might consider short term LCDs for management of type 2 diabetes, while actively monitoring and adjusting diabetes medication as needed.”

“Future long term, well designed, calorie controlled randomised trials are needed to determine the effects of LCD on sustained weight loss and remission of diabetes, as well as cardiovascular mortality and major morbidity,” they conclude.

 

Study details

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

Joshua Z Goldenberg, Andrew Day, Grant D Brinkworth, Junko Sato, Satoru Yamada, Tommy Jönsson, Jennifer Beardsley, Jeffrey A Johnson, Lehana Thabane, Bradley C Johnston

Published in BMJ on 13 January 2021

Abstract

Objective
To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes.

Design
Systematic review and meta-analysis.

Data sources
Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020.

Study selection
Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible.

Data extraction
Primary outcomes were remission of diabetes (HbA1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA1c, fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist.

Results
Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I2=58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA1c <6.5% without medication was used. Subgroup assessments determined as meeting credibility criteria indicated that remission with LCDs markedly decreased in studies that included patients using insulin. At 12 months, data on remission were sparse, ranging from a small effect to a trivial increased risk of diabetes. Large clinically important improvements were seen in weight loss, triglycerides, and insulin sensitivity at six months, which diminished at 12 months. On the basis of subgroup assessments deemed credible, VLCDs were less effective than less restrictive LCDs for weight loss at six months. However, this effect was explained by diet adherence. That is, among highly adherent patients on VLCDs, a clinically important reduction in weight was seen compared with studies with less adherent patients on VLCDs. Participants experienced no significant difference in quality of life at six months but did experience clinically important, but not statistically significant, worsening of quality of life and low density lipoprotein cholesterol at 12 months. Otherwise, no significant or clinically important between group differences were found in terms of adverse events or blood lipids at six and 12 months.

Conclusions
On the basis of moderate to low certainty evidence, patients adhering to an LCD for six months may experience remission of diabetes without adverse consequences. Limitations include continued debate around what constitutes remission of diabetes, as well as the efficacy, safety, and dietary satisfaction of longer term LCDs.

 

BMJ study (Open access)

 

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