Low and Very Low Carb Diets for Type 2 Diabetes Remission

Weight loss is the most effective way to put diabetes into remission. The DiRECT trial used a low-calorie liquid diet to show an 86% remission rate (HbA1c <6.5%) in those losing 15 kg or more.¹

A low-carbohydrate diet (keto diet) is another way to lose weight quickly. By avoiding carbohydrates, the body turns to fat as the main energy source. This meta-analysis evaluated 23 studies and found a 32% diabetes remission rate (HbA1c <6.5%) when this diet was used for 6 months. The short-term risks were minimal, with a small increase in LDL cholesterol. The benefits were the weight loss and a decrease in triglycerides. There was no change in C-reactive protein. The fact that this inflammatory marker did not change suggests that weight loss balances the proinflammatory effect of eating more fat.

The concern is long-term sustainability and risk. It is difficult to sustain a low-carbohydrate diet over time, and this meta-analysis showed an erosion of the effect after 12 months. The keto diet replaces carbohydrates with fat. And multiple studies have shown that, if that fat comes from animals with four legs, the risk of systemic inflammation and cardiovascular events go up. In fact, another meta-analysis has shown a higher mortality risk with prolonged adherence to keto diets.²

What to Recommend

Six months of a low-carbohydrate, keto diet is an effective and safe way to lose weight with the potential of reversing diabetes. After 6 months, encourage transition to a high-fiber, plant-based diet with fish to help sustain weight loss and reduce the risk of cardiovascular events in the long term.³

References

1. Lean MEJ, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019;7(5):344-355. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30068-3/fulltext
2. Seidelmann SB, Claggett B, Cheng S, et al. Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. Lancet Public Health. 2018;3(9):e419-e428. https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(18)30135-X/fulltext
3. Petermann-Rocha F, Parra-Soto S, Gray S, et al. Vegetarians, fish, poultry, and meat-eaters: who has higher risk of cardiovascular disease incidence and mortality? A prospective study from UK Biobank. Eur Heart J. 2020 Dec 14. DOI: 1093/eurheartj/ehaa939. Online ahead of print. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa939/6032616

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.

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