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[Nutrition Research Review] Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomised trial data

Diabetes Mellitus is estimated to affect 1 in 11 adults worldwide and is associated with 11 per cent of deaths annually. Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes and has been associated with genetic, lifestyle, and body weight risk factors.

T2DM is characterised by insulin resistance, and as such, prior to the discovery of insulin, dietary reduction of carbohydrates was a common management strategy. Current management recommendations involve pharmaceutical management, achieving glycaemic control, and the use of structured diets that include various percentages of energy from carbohydrates.

In recent years, there has been a renewed interest in carbohydrate restriction as a T2DM dietary management strategy, although concerns regarding long term safety remain (Seidelmann et al., 2018).

This systematic review and meta-analysis explores the effect of Low Carbohydrate Diets (LCD) on the remission of T2DM (as defined by HbA1c <6.5% or fasting glucose <7.0 mmol/L), as well as a range of other outcome measures including weight loss, HbA1c, fasting glucose, health-related Quality of Life (QoL), medication reduction, adverse events, and blood lipids (Goldenberg et al., 2021).

Drawing from both published and unpublished data, results from 23 studies (14 including patients using Insulin) involving 1,357 patients, mostly those living in larger bodies, aged between 47 and 67 years were included. Carbohydrate intake was classified as low if it was <26 per cent calories from carbohydrates or <130 g per day.

The main intervention comparison in included studies was a low-fat diet (78%), 61 per cent of included trials included participants using insulin and 52 per cent met criteria for a very LCH (i.e., <10% daily calories from carbohydrates). It is noted that 78 per cent of the trials were impacted by participant drop out.

Findings

Eight studies reported on remission at six months and when using the HbA1c <6.5 per cent criteria (independent of medication) LCD’s increased rates of remission by an extra 32 patients per 100 patients followed (risk difference 0.32; 95% CI: 0.17 to 0.47; GRADE=moderate). When medication use was removed, this risk reduction was lower (risk difference 0.05; -0.05 to 0.14; GRADE=low).

Three studies reported on remission at 12 months, HbA1c <6.5 per cent criteria (independent of medication) LCD’s increased rates of remission (risk difference 0.10; -0.02 to 0.21, GRADE=moderate). When medication use was removed, remission rates were lower (risk difference -0.04; -0.16 to 0.09; GRADE=low).

Eighteen studies reported on weight loss at six months and analysis found that LCDs were associated with a greater amount of weight loss versus control diets (mean difference -3.46, 95% CI: -5.25 to -1.67, GRADE=moderate). However, data from the seven studies that included a measure of weight loss at twelve months, demonstrated no significant advantage of the LCD over comparison diets. This is in line with current evidence identifying a pattern of weight regain over time following non-surgical diet and lifestyle weight management interventions (Nordmo et al., 2020).

At six months there were improvements in HbA1c, fasting glucose, medication usage, triglycerides and insulin sensitivity associated with the LCD. However, again, these improvements either diminished, or were no longer present, by 12 months.

While there were no significant differences in health-related QoL and low-density lipoprotein cholesterol at six months, at 12 months the LCD was associated with a clinically important decline in health-related QoL and worsening of low-density lipoprotein cholesterol.

Adverse events were reported for 11 studies at six months with analysis finding a small increased risk of total adverse events associated with the LCD (risk difference 0.04; -0.01 to 0.08; GRADE= very low). Analysis of the results of the three studies that reported total adverse events at 12 months found the LCD to be associated with a small, trivial decrease (risk difference -0.05; -0.24 to 0.14; GRADE= very low).

Strengths identified in this study include the inclusion of unpublished data, the use of robust methods, the use of GRADE for rating the certainty of evidence, and the consideration given to minimally clinically important differences.

Limitations identified include that the definition of remission in T2DM is debated, the lack of consideration or quantification of any potential benefits flowing from caloric restriction (vs. carbohydrate restriction), the use of short-term markers, and the poor reporting of included trials on adverse events thus limiting conclusions drawn about LCD safety.

Importantly, the authors note that as most studies included in the review and meta-analysis used the low-fat diet as a comparator, this precludes a comparison of the benefits of the LCD to the Mediterranean Diet in T2DM, a dietary pattern that is also suggested as being of clinical benefit in T2DM (Martín-Peláez et al., 2020). Similarly, studies did not report on macronutrient quality which has been found to be relevant (Seidelmann et al., 2018).

Conclusions

There appears to be improved rates of remission of T2DM and no adverse effects following a LCD compared to a low-fat diet for six months, although benefits diminish by 12 months. However, the worsening of QoL and low-density lipoprotein cholesterol seen at 12 months suggests that longer term LCDs may not be ideal. The authors suggest that clinicians may consider using a LCD as a short term intervention for T2DM management, with appropriate monitoring and medication adjustment.

See the full article here.

Anna Millichamp, APD, Senior Teaching Fellow, Bond University

Learn more in the online Professional Diploma of Medical Nutrition Management.

References

1. Seidelmann, S. B., Claggett, B., Cheng, S., Henglin, M., Shah, A., Steffen, L. M., Folson, A. R., Rimm, E. B., Willett, W. C., & Solomon, S. D. (2018). Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. The Lancet Public Health, 3(9), e419-e428.

    

2. Goldenberg, J. Z., Day, A., Brinkworth, G. D., Sato, J., Yamada, S., Jönsson, T., … & Johnston, B. C. (2021). 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, 372.

    

3. Nordmo, M., Danielsen, Y. S., & Nordmo, M. (2020). The challenge of keeping it off, a descriptive systematic review of high‐quality, follow‐up studies of obesity treatments. Obesity Reviews, 21(1), e12949.

    

4. Martín-Peláez, S., Fito, M., & Castaner, O. (2020). Mediterranean diet effects on type 2 diabetes prevention, disease progression, and related mechanisms. A review. Nutrients, 12(8), 2236.

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