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low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data

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 (HbA 1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA 1c , 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 HbA 1c <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, I 2 =58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA 1c <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. Systematic review registration PROSPERO CRD42020161795.

Improvement of Diabetes Mellitus After Colorectal Cancer Surgery: A Retrospective Study of Predictive Factors For Type 2 Diabetes Mellitus Remission and Overall Survival

“…For patients with T2DM, lifestyle changes might also benefit T2DM remission. Patients adhering to low-carbohydrate diets and low-energy diets could experience T2DM remission (20). Increased physical activities could be a predictor for T2DM remission (21).…”

A Preliminary Study Showing the Impact of Genetic and Dietary Factors on GC–MS-Based Plasma Metabolome of Patients with and without PROX1-Genetic Predisposition to T2DM up to 5 Years Prior to Prediabetes Appearance

“…As the role of dietary carbohydrates in the development and maintenance of T2DM receives now increasing attention [29], the participants of this study underwent an HC-meal challenge test. The progress of T2DM is often explained by excessive consumption of high-carbohydrates and high-calorie diets [30]. There is a lot of systematic reviews and meta-analyses describing the effect of low carbohydrate diet [29,30] in comparison to normal or high carbohydrate diet [11,27,31] in patients with T2DM, but only some of these studies described the post-meal changes in patients with a genetic predisposition to T2DM [1,11,27].…”

Effects of a Self-Prepared Carbohydrate-Reduced High-Protein Diet on Cardiovascular Disease Risk Markers in Patients with Type 2 Diabetes

“…The conclusion of one meta-analysis of data from 13 studies (lasting from 3 months to 1 year) evaluating the metabolic effects of diet treatment in 1138 patients with T2DM suggested that low-carbohydrate high-protein diets do not improve HDL cholesterol but decrease TG concentration [ 28 ]. However, another meta-analysis of 23 trials (lasting from 3 months to 2 years) in 1357 participants with T2DM reported a significant decrease in TG concentration coupled with a near significant increase in HDL cholesterol after 6 and 12 months on a low-carbohydrate diet [ 14 ]. In addition, another meta-analysis of 19 shorter trials (lasting from 10 days to 6 weeks) in 306 patients with T2DM concluded that low-carbohydrate diets decrease TG and increase HDL cholesterol compared with low-fat diets [ 29 ].…”

“…Accordingly, weight loss is the cornerstone of T2DM lifestyle management [ 12 ], but scientific evidence for the optimal dietary treatment of T2DM is lacking. The most recent American Diabetes Association recommendations suggest low-carbohydrate and very-low-carbohydrate diets as a viable treatment strategy for some individuals with T2DM [ 13 ], even if these diets do not necessarily lead to greater weight loss compared with other hypocaloric regimens [ 14 , 15 ]. Carbohydrate-reduced, high-protein (CRHP), non-ketogenic diets induce beneficial effects on glucose control in individuals with T2DM even in the absence of weight loss, and are thus being advocated to ameliorate hyperglycemia [ 16 , 17 , 18 , 19 ].…”