Low carb and Type 2 diabetes – the underappreciated importance of reduced medication requirements

14th November 2019

Author: Sean Wheatley/14 November 2019/Categories: , Research

Dr. Sean Wheatley, PhD – Science and Research Lead

 

A growing body of evidence is showing that low carb approaches can be an effective option for people with Type 2 diabetes, and an increasing number of influential organisations, such as Diabetes UK1 and the American Diabetes Association2, are supporting their use. This is great, as the more options people have the more likely it is they will be able to find a solution that is right for them. Much of this research, on the face of it, suggests a superiority of low carbohydrate diets in the short term but little difference between low carb approaches and other ways of eating over a longer duration. One thing that is often not fully considered in these studies though is the effect of different dietary approaches on the medication requirements of those following them – an omission that may have a major influence on the conclusions.

 

Why is this important?

Firstly, many people with Type 2 diabetes take one or more medications to help manage their blood glucose levels, and the prospect of reducing the amount they need to take is a major motivator for many people to make lifestyle changes. The ability to reduce medication requirements is therefore a massive plus point for any intervention that can achieve this.

Secondly, if changes in medication aren’t considered when we are comparing two different diets then we aren’t really getting a true picture of their relative effects. If two dietary approaches achieve similar changes in blood glucose control but in one group there is also a greatly reduced requirement for medication, then there is a clear difference in the effect of these approaches despite a seemingly similar change in blood glucose levels.

 

What does the evidence show?

Systematic reviews and meta-analyses

There are, to my knowledge, 11 systematic reviews comparing low carbohydrate dietary approaches with other ways of eating in people with Type 2 diabetes that also included meta-analyses3-13. Meta-analyses are a statistical method for pooling the results of studies to look at the overall effects. In the 11 identified the conclusions reached are mostly similar to those outlined in the opening paragraph, though it is beyond the scope of this blog to fully discuss their findings and their possible limitations.

Meta-analyses can be very useful, and are in fact considered the highest quality level of evidence we have (if there is enough qualifying research of a high enough quality and the meta-analysis is performed well). It can be difficult to fully account for all the different things that might affect the outcomes in these typed of analyses though. Ideally, from the 11 reviews considered here we only want to know what the effect of the diet was. So if there are other things influencing the results then this means the conclusions won’t be truly correct. Changes in medication use are one of the main things that can also affect the outcomes in these reviews, as they can dramatically change the main outcome (HbA1c, an indicator of blood glucose control, in this case). None of the identified meta-analyses fully account for the possible influence of medications.

What makes it difficult to account for changes in medication in meta-analyses is that there isn’t a uniform way for this to be recorded. If the different studies don’t report something in the same way there is no simple way to try and account for it in the meta-analysis. Essentially this means you can’t truly control for the effects of medication in meta-analyses, so instead you have to look at the individual studies and try to reach a conclusion this way. When medication changes were discussed in this way within the 11 systematic reviews/meta-analyses (they weren’t discussed at all in many of them), the following was reported:

 

  • Snorgaard et al (2017)7 found that, in the seven studies they included which reported relevant outcomes, medication was reduced at three and six months with lower carbohydrate dietary approaches compared to higher carbohydrate dietary approaches; and was “numerically lower” at 12 months. The authors acknowledged that “changes in glucose lowering medication have probably led to an underestimation of the effect of low carb diets on glycaemic control”
  • Sainsbury et al (2018)9 found that, in the 12 studies they included which reported relevant outcomes, there was a greater reduction in medication use for participants on carbohydrate-restricted dietary approaches compared with higher carbohydrate dietary approaches at every time point; with all studies that reported on such outcomes observing either reduced dosage of oral medications and/or insulin or an elimination of medication altogether
  • van Zuuren et al (2018)10 reported that “in all of the studies that included patients taking medication and that adequately reported eventual adaptations, with the exception of one,  glucose lowering drug doses were reduced in participants who consumed low-carbohydrate food, but not in those consuming low-fat food.” (though this was only based on four studies)
  • Korsmo-Haugen et al (2018)11 concluded that the information available suggests that there was a greater reduction in the use of diabetes medication, particularly insulin, in the low carbohydrate groups – and that this may have masked a more positive influence of low carbohydrate diets on glycaemic control. They again acknowledged that this conclusion was based on limited information however, with only four studies showing a significant difference in the change in medications between diets
  • Huntriss et al (2018)12 found that, in the 14 studies they included which reported relevant outcomes, every study reported a greater reduction in the requirement for diabetes medication in the low carbohydrate group than the control group. Of the 11 studies that ran relevant analyses nine (82%) found this difference to be statistically significant 

 

There is of course an overlap in the studies used within some of the reviews above, and this simplistic discussion doesn’t factor in how big or small the changes were, but these findings are remarkably clear and consistent.

 

Randomised controlled trials (RCTs)

As alluded to above there are additional limitations with these meta-analyses, one of which is that many of the included studies do not define a low carbohydrate diet in a way consistent with what most people would consider to truly be low carb (the most commonly applied definition of “low carb” is less than 130g carbs, or less than 26% total energy from carbs, each day14). Even where the included studies have the intention for the low carb group to consume below these thresholds, in some cases the actual recorded carb intake ends up being much higher than this.

Of the studies included in the 11 identified meta-analyses only nine papers15-23, representing six studies, included low carb groups which had a mean reported carb intake that met the definition above and which had more than 50 participants (plus one study was removed as it assessed protein shakes rather than dietary approaches24, and another was omitted as the control group actually had less carbs than the low carb group at multiple time points25)*. One of the six studies had a more recent paper published26 which was included here too, taking the total to 10 papers from 6 studies.

Once again it is beyond the scope of this blog to discuss the outcomes of these studies and any possible limitations in detail, but the findings once more mostly showed short-term superiority for low carb and little difference between studies longer-term (though where there were differences they invariable favoured lower carb intakes). Importantly though, five of the six studies reported on medication changes (only the study represented by Stern et al 200416 didn’t) and in all five there was a greater reduction in diabetes medication requirements in the participants following a low carbohydrate diet than there was in those consuming the control diets (which were usually based around a low fat diet).

 

Other evidence

Beyond RCTs there are other sources of evidence, which are perhaps more reflective of the real world (in part because the participants have chosen to follow a low carb diet rather than being randomised to one) which also demonstrate important reductions in medication needs when carbs are restricted.  For example:

 

  • Virta Health showed that, in participants who severely restricted carbohydrates (to below 30g/day in most cases), 67% of all diabetes medications were no longer required after two years27. Additionally, mean insulin dose was decreased by 81% (from 81.9 units/day to 15.5) and over 60% of those using insulin at baseline in the low carb group (n=57) were able to omit it altogether. In the usual care group mean insulin dose actually increased
  • In a sample of 1,000 participants of the Low Carb Program, 289 (40.4%) of the 714 participants who were taking at least one medication to manage their diabetes at baseline were able to reduce at least one of them28

 

Medication reduction is not limited to diabetes medications either, with, for example, 35 (21.5%) of 163 hypertension drugs (which were being prescribed to 154 patients who opted to restrict their carbohydrate intake for, on average, two years; in a primary care setting) being de-prescribed29.

 

Practical application

As mentioned before, the ability to reduce medication use is a strong motivator for many individuals. This is particularly true for insulin users, as the administration of insulin can cause significant discomfort, it increases risk of hypos**, and it can lead to difficulties with weight management. Patients should be provided with the appropriate information to make an informed choice about what is the right approach for them, and the evidence around potentially reduced medication requirements when adopting a low carbohydrate dietary approach should form part of this discussion.

Importantly, the requirement for many common diabetes medications is reduced or removed on day one of a low carb diet. This is a positive thing for the patients, but it also means it is essential to have a medication review BEFORE starting a low carbohydrate diet. An excellent practical guide for healthcare professionals to support this adjustment of medications is now available.30 Further information and guidance for healthcare professionals looking to support their patients in the adoption of a low carb way of eating, including but not limited to information on medication adjustments, can be found here.

A secondary benefit of reduced medication requirements is a reduced spend on diabetes medication, as demonstrated by Dr David Unwin in his GP practice in Norwood31; though this is also beyond the scope of this blog.

 

So what’s the bottom line?

Where an outcome such as blood glucose is similar between two groups, but one group has achieved this whilst significantly reducing the amount of medication they require, this demonstrates a superior performance from the intervention that allowed this. This is consistently the case for low carb diets when compared to other ways of eating. Therefore, the failure of many studies and reviews to effectively consider the influence of changes in medication use penalises the low carbohydrate groups, resulting in an underestimation of its benefits for many people.

Beyond this, the ability to reduce diabetes medication requirements is an important outcome in itself; as many people identify a desire to reduce their meds as their primary motivation for wanting to make some lifestyle changes. Whether or not it is superior to other ways of eating, there is clear evidence that low carbohydrate dietary approaches should be offered as a possible option to people with Type 2 diabetes.

 

 

* Further details of these studies and the process used for identifying and filtering them are included in the upcoming X-PERT Health position statement on the use of low carbohdyrate diets for people with Type 2 diabetes. If you would like to be made aware when this has been released please contact me at the email address below

** Despite some concerns hypo risk is reduced on low carbohydrate diets, as long as an appropriate medication review is performed, as the two main medications that increase hypo risk (insulin and sulphonylureas) are reduced or removed when following one. There were no reported severe hypoglycaemic events in the RCTs mentioned in this blog

 

 

As with all our blogs and other work we’d love to hear your thoughts and feedback, so feel free to leave a comment on our Facebook page, drop me an e-mail at sean.wheatley@xperthealth.org.uk, or tweet us/me at @XPERTHealth or @SWheatley88. If you have attended an X-PERT Programme or are an X-PERT Educator you can also register for our free online forum.

 

 

References

1.            Diabetes UK. Evidence-based nutrition guidelines for the prevention and management of diabetes. Diabetes UK; 2018.

2.            Evert AB, Dennison M, Gardner CD, Garvey WT, Lau KHK, MacLeod J, et al. Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report. Diabetes Care. 2019;42(5):731-54.

3.            Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Sato M, et al. Influence of fat and carbohydrate proportions on the metabolic profile in patients with type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32(5):959-65.

4.            Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. The American journal of clinical nutrition. 2013;97(3):505-16.

5.            Naude CE, Schoonees A, Senekal M, Young T, Garner P, Volmink J. Low carbohydrate versus isoenergetic balanced diets for reducing weight and cardiovascular risk: a systematic review and meta-analysis. PLoS One. 2014;9(7):e100652.

6.            Fan Y, Di H, Chen G, Mao X, Liu C. Effects of low carbohydrate diets in individuals with type 2 diabetes: Systematic review and meta-analysis. Int J Clin Exp Med. 2016;9(6):11166-74.

7.            Snorgaard O, Poulsen GM, Andersen HK, Astrup A. Systematic review and meta-analysis of dietary carbohydrate restriction in patients with type 2 diabetes. BMJ Open Diabetes Research & Care. 2017;5(1):e000354.

8.            Meng Y, Bai H, Wang S, Li Z, Wang Q, Chen L. Efficacy of Low Carbohydrate Diet for Type 2 Diabetes Mellitus Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diabetes Research and Clinical Practice. 2017;131:124-31.

9.            Sainsbury E, Kizirian NV, Partridge SR, Gill T, Colagiuri S, Gibson AA. Effect of dietary carbohydrate restriction on glycemic control in adults with diabetes: A systematic review and meta-analysis. Diabetes Research and Clinical Practice. 2018;139:239-52.

10.          van Zuuren EJ, Fedorowicz Z, Kuijpers T, Pijl H. Effects of low-carbohydrate- compared with low-fat-diet interventions on metabolic control in people with type 2 diabetes: a systematic review including GRADE assessments. The American journal of clinical nutrition. 2018;108:1-32.

11.          Korsmo-Haugen HK, Brurberg KG, Mann J, Aas AM. Carbohydrate quantity in the dietary management of type 2 diabetes - a systematic review and meta-analysis. Diabetes, obesity & metabolism. 2018;21(1):15-27.

12.          Huntriss R, Campbell M, Bedwell C. The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. European Journal of Clinical Nutrition. 2018;72(3):311-25.

13.          McArdle PD, Greenfield SM, Rilstone SK, Narendran P, Haque MS, Gill PS. Carbohydrate restriction for glycaemic control in Type 2 diabetes: a systematic review and meta-analysis. Diabetic Medicine. 2019;36(3):335-48.

14.          Feinman RD, Pogozelski WK, Astrup A, Bernstein RK, Fine EJ, Westman EC, et al. Dietary Carbohydrate restriction as the first approach in diabetes management. Critical review and evidence base. Nutrition. 2015;31(1):1-13.

15.          Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. The New England journal of medicine. 2003;348(21):2074-81.

16.          Stern L, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, et al. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med. 2004;140(10):778-85.

17.          Daly ME, Paisey R, Paisey R, Millward BA, Eccles C, Williams K, et al. Short-term effects of severe dietary carbohydrate-restriction advice in Type 2 diabetes—a randomized controlled trial. Diabetic Medicine. 2006;23(1):15-20.

18.          Westman EC, Yancy WS, Jr., Mavropoulos JC, Marquart M, McDuffie JR. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 2008;5:36.

19.          Goldstein T, Kark JD, Berry EM, Adler B, Ziv E, Raz I. The effect of a low carbohydrate energy-unrestricted diet on weight loss in obese type 2 diabetes patients – A randomized controlled trial. e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism. 2011;6(4):e178-e86.

20.          Guldbrand H, Dizdar B, Bunjaku B, Lindström T, Bachrach-Lindström M, Fredrikson M, et al. In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss. Diabetologia. 2012;55(8):2118-27.

21.          Jonasson L, Guldbrand H, Lundberg AK, Nystrom FH. Advice to follow a low-carbohydrate diet has a favourable impact on low-grade inflammation in type 2 diabetes compared with advice to follow a low-fat diet. Annals of medicine. 2014;46(3):182-7.

22.          Tay J, Natalie D L-M, Thompson CH, Noakes M, Buckley JD, Wittert GA, et al. A Very Low Carbohydrate, Low Saturated Fat Diet for Type 2 Diabetes Management: A Randomized Trial. Diabetes Care. 2014;37:2909–18.

23.          Tay J, Luscombe-Marsh ND, Thompson CH, Noakes M, Buckley JD, Wittert GA, et al. Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial. The American journal of clinical nutrition. 2015;102:780–90.

24.          Goday A, Bellido D, Sajoux I, Crujeiras AB, Burguera B, Garcia-Luna PP, et al. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutrition & Diabetes. 2016;6:e230.

25.          Iqbal N, Vetter ML, Moore RH, Chittams JL, Dalton-Bakes CV, Dowd M, et al. Effects of a low-intensity intervention that prescribed a low-carbohydrate vs. a low-fat diet in obese, diabetic participants. Obesity (Silver Spring). 2010;18(9):1733-8.

26.          Tay J, Thompson CH, Luscombe-Marsh ND, Wycherley TP, Noakes M, Buckley JD, et al. Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high carbohydrate, low fat diet in type 2 diabetes: a 2 year randomized clinical trial. Diabetes, obesity & metabolism. 2018;20(4):858-71.

27.          Athinarayanan SJ, Adams RN, Hallberg SJ, Mckenzie AL, Bhanpuri NH, Campbell WW, et al. Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-year Non-randomized Clinical Trial. Frontiers in Endocrinology. 2018;10:348.

28.          Saslow LR, Mason AE, Kim S, Goldman V, Ploutz-Snyder R, Bayandorian H, et al. An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial. J Med Internet Res. 2017;19(2):e36.

29.          Unwin DJ, Tobin SD, Murray SW, Delon C, Brady AJ. Substantial and Sustained Improvements in Blood Pressure, Weight and Lipid Profiles from a Carbohydrate Restricted Diet: An Observational Study of Insulin Resistant Patients in Primary Care. International Journal of Environmental Research and Public Health. 2019;16(15):2680.

30.          Murdoch C, Unwin D, Cavan D, Cucuzzella M, Patel M. Adapting diabetes medication for low carbohydrate management of type 2 diabetes: a practical guide. British Journal of General Practice. 2019;69(684):360-1.

31.          Unwin D, Haslam D, Livesey G. It is the glycaemic response to, not the carbohydrate content of food that matters in diabetes and obesity: The glycaemic index revisited. Journal of Insulin Resistance. 2016;1(1):1-9.

 

 

 

 

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