Very Low-Calorie Diet May Trigger Type 2 Diabetes Remission

Miriam E Tucker

March 28, 2016

Type 2 diabetes is potentially reversible via an 8-week, very low-calorie diet followed by careful weight management for up to 6 months, new research shows.

The findings were published online March 21, 2016 in Diabetes Care by Dr Sarah Steven of Newcastle University, United Kingdom, and colleagues.

"At the time of diagnosis, everyone should be told that type 2 diabetes is potentially reversible by substantial weight loss. For people with type 2 diabetes who resent their loss of health, there is a genuine way out. It's not an easy option but to be carefully considered, planned, and discussed with spouse or partner," lead investigator Dr Roy Taylor, also of Newcastle University, told Medscape Medical News.

In the study of 30 overweight or obese adults with type 2 diabetes of durations from 6 months to 23 years, weight fell significantly following an 8-week mostly liquid diet of 600 to 700 calories a day, and 12 of the 30 individuals (40%) achieved an average fasting plasma glucose (FPG) level of less than 126 mg/dL.

After a further 6 months of an intensive, individualized weight-management program, 13 of 30 (43%) maintained an FPG below 126 mg/dL while off all glucose-lowering medications.

"Substantial weight loss can be achieved only by severe calorie restriction….The transition from low-calorie liquid diet to normal eating requires very careful management. This two-step approach to substantial weight loss is successful, unlike current beliefs about how to lose weight," Dr Taylor said.

But obesity expert Arya M Sharma, MD, from University of Alberta, Edmonton, is skeptical: "The fact that a low-calorie diet can reverse diabetes is something we've known a long time….The key issue here is not whether weight loss can actually reverse diabetes or put it into remission but the durability of the effect….As far as obesity-management trials, 6 months is not long."

Dr Sharma added, "It's a proof-of-principle study showing that if you lose weight through a diet, there's a good chance your diabetes will go into remission. But by the same note, if you put the weight back on, your diabetes is going to come back."

Two-Step Process

The 8-week very low-calorie diet consisted of a three-times daily liquid formula containing 43% carbohydrates, 34% protein, and 19.5% fat, providing about 624 kcal/day. Subjects were also allowed to eat nonstarchy vegetables and were encouraged to drink at least 2 L/day of calorie-free beverages and to maintain normal activities. One-to-one support was provided via telephone, email, text messages, or face-to-face contact.

After the 8 weeks, solid food was gradually introduced in weight-maintaining quantities (approximately 1600 to 2000 kcal per day, although the focus was on weight of food portions).

Studies were conducted a minimum of 6 days after full return to solid foods. Diabetes remission was defined as an FPG of less than 126 mg/dL, and that level was used to define "responders" to the very low-calorie diet.

During the 6-month weight-maintenance phase, participants received a structured individualized program that included goal setting, action planning, and barrier identification, with monthly reviews.

Subjects with fasting glucose levels exceeding 180 mg/dL on two occasions were put on glucose-lowering medications. Only one patient was excluded after (deliberately) not achieving the minimum 3.8% weight-loss target, leaving 29 in the final sample.

Reversing Diabetes

For the entire group, weight fell from 98.0 kg at baseline to 83.8 kg during the very low-calorie diet (P < .001) and remained at 84.7 kg after 6 months.

The participants who achieved the FPG of less than 126 mg/dL after return to weight-maintaining solid food were dubbed responders.

In the responders, FPG fell from 160 mg/dL to 112 mg/dL (P = .002) in the maintenance phase and remained constant at about 111.6 mg/dL without any glucose-lowering drugs. In nonresponders, FPG fell from 238 mg/dL to 196 mg/dL (P = .016) and remained constant at 169.2 mg/dL.

The rise in FPG over the 2 weeks from the end of the very low-calorie diet to establishment on an isocaloric diet was significantly greater in nonresponders, of whom six restarted diabetes medications during the 6-month maintenance period.

HbA1c remained stable throughout the 6-month period in both groups (responders 5.8% to 5.9%, P = .540, and nonresponders 8.0% to 7.8%, P = .481).

Both responders and nonresponders maintained significant improvements in blood pressure, triglycerides, and non-HDL cholesterol levels after the very low-calorie diet and maintained those levels over the 6-month maintenance period.

Responders vs Nonresponders

Achieved weight loss after the very low-calorie diet was similar between the responders and nonresponders (15.8% vs 13.6%, P = 0.06), and weight remained constant over 6 months in both groups.

The responders had a shorter diabetes duration (3.8 vs. 9.8 years, P = .007) and were younger (52.0 vs. 59.9, P = .032) than nonresponders. Responders also had lower fasting glucose levels (P < .001) and higher serum insulin levels at baseline (P = 0.005) and achieved fasting glucose level correlated positively with diabetes duration (P = .001).

Plasma insulin levels fell in both groups after the very low-calorie diet and remained stable throughout the weight-maintenance phase.

First-phase insulin response was markedly reduced at baseline in nonresponders compared with responders (P = .002). The response improved in the responders (P = .03), and there was a small increase in the nonresponders (P = .04). First-phase insulin secretion did not change over the weight-maintenance period in either responders or nonresponders.

"The people with very long duration of diabetes simply did not return to nondiabetic blood sugar levels. We showed that this was due to their pancreases having passed a point of no return — after 10 or more years of diabetes their insulin-producing cells had truly failed. However, this process of failure is stopped in its tracks by the weight loss," Dr Taylor commented.

But Is This a Practical Approach? Only Time will Tell

Dr Sharma doesn't disagree with the findings but simply doubts this is achievable for most people.

"This is not a real-life study. This is a proof-of-principle study that reminds us that weight loss can lead to remission of diabetes. What it really points us to is the need for better obesity treatments. Although this treatment was effective in this study, it's not a practical approach for treating obesity in the long term."

Nonetheless, at least two other studies using the very low-calorie approach are ongoing, both of them funded by the commercial Cambridge Weight Plan.

The Diabetes Remission Clinical Trial (DIRECT), from Dr Taylor's group, will randomize about 150 obese people with type 2 diabetes to either an 800-kcal/day liquid diet or usual care for 8 to 20 weeks, followed by food reintroduction and a 2-year observation period to document durability.

The other, larger study, called PREVIEW, is investigating a similar approach in more than 2000 adults with prediabetes in eight European centers. That study starts with an 800- to 1000-kcal/day diet, and those who lose at least 8% of their initial weight will enter weight-loss maintenance programs. Results from that study, funded by an EU grant, are expected in 2018.

The current study was funded by a National Institute of Health Research Newcastle Biomedical Research Center Grant and a Novo Nordisk UK Research Foundation Research Fellowship. The funders had no input on any aspect of the study design or writing. Nestle UK provided OPTIFAST on request but had no other input on the research. Dr Taylor has received lecture fees from Novartis, Novo Nordisk, and Lilly and for contribution to running a European Association for the Study of Diabetes workshop from Nestle. The coauthors have no relevant financial relationships. Dr Sharma serves as an advisor/consultant for Novo Nordisk, Takeda, Ethicon, and Zafgen.

Diabetes Care. Published online March 21, 2016. Abstract

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