Wednesday, March 5, 2014

Can intermittent very-low-calorie dieting cure diabetes?

The health effects of very-low-calorie diets (VLCDs) adopted for short periods of time (e.g., 5 days) have been the target of much recent in the past. Consuming 400-600 kcal/day would be considered VLCDing. VLCDing for significantly longer periods of time than 5 days can be dangerous, and in some cases potentially fatal. Nevertheless, there is speculation that it can also cure type II diabetes ().

Intermittent VLCDs mimic in part what probably happened with our ancestors in our evolutionary past. Successful hunting and gathering would lead to weight-maintenance food intake most of the time, with occasional periods of severe food scarcity. This has probably been a regular pattern in our evolutionary history, leading to health-promoting adaptations that are triggered by VLCDs.

The part that VLCDs alone do not mimic is the “hunting and gathering part”, or the exercise required to obtain food when it is scarce. This is an important point, because VLCDs are likely to induce lean body mass loss without exercise, together with body fat loss. VLCDs without exercise are not very natural, even though they can have very positive effects on one’s health, as we’ll see below.

An interesting and well cited study of the effects of VLCDs in participants with type II diabetes was published in 1998 in an article authored by Katherine V. Williams and colleagues (). The study included 54 participants, and lasted 20 weeks in total. The site of the study was the University of Pittsburgh School of Medicine. The participants were split in three groups, referred to as:

- Standard behavioral therapy (SBT). The participants received a 1,500−1,800 kcal/day diet throughout, with the goal of inducing gradual weight loss.

- Intermittent 1 day/week VLCD (one-day). The participants received a VLCD for 5 consecutive days during week 2, followed by an intermittent VLCD therapy for 1 day/week for 15 weeks, with a 1,500−1,800 kcal/day diet at other times.

- Intermittent 5 day/week VLCD (five-day). The participants received a VLCD for 5 consecutive days during week 2, followed by an intermittent VLCD therapy for 5 consecutive days every 5 weeks (5-day), with a 1,500−1,800 kcal/day diet at other times.

There is a reason behind this complicated arrangement. The researchers wanted to make sure that the average caloric intake for the two VLCD groups was identical, but 18,000-28,000 kcal lower than for the SBT group. The SBT group served as a baseline group.

All of the three diets were designed to make the participants lose weight. Exercise was not manipulated as part of the experiment. The one-day and five-day groups consumed 400-600 kcal/day while VLCDing, with the majority of the calories coming from high-protein-low-fat minimally processed food items – notably lean meat, fish, and fowl.

The graphs below show results in terms of weight loss and fasting plasma glucose (FPG) reduction. They suggest that, while there were significant differences in weight loss between the VLCD groups and the SBT group, the differences in FPG reduction were relatively minor across the three groups.

Glucose was measured in mmol/l and weight in kg. One mmol/l is equivalent to approximately 18 mg/dl (), and one kg is equivalent to about 2.2 lbs.

The graph below, however, shows a different picture. It shows results in terms of the percentages of participants with HbA1c below 6 percent. The HbA1c is a measure of average blood glucose over a period of a few months ().

The graph above tells us that the intermittent VLCD interventions, particularly the second (five-day), were reasonably successful at promoting average blood glucose control. A threshold normally used to characterize poor blood glucose control is 7.3 percent (), which is based on studies of HbA1c levels associated with diabetes complications.

The graph below, which is probably the most telling of all, shows long-term FPG changes (at the 20-week mark) plotted against short-term changes (at the 3-week mark). What this graph tells us is that those who experienced the most improvement right away were the ones with the most improvement in the long term.

This study tells us a few interesting things. Firstly, intermittent VLCDing with a focus on high-protein foods (lean meats) seems to be a powerful way of controlling average blood glucose levels in diabetics. It is essentially a low carbohydrate diet that is also low in calories (). Secondly, results with respect to FPG levels are not as telling as those in terms of HbA1c levels, even though HbA1c and FPG are highly correlated.

Thirdly, intermittent VLCDing may not actually “cure” diabetes when significant beta cell damage has already occurred (). This conclusion is speculative, but it follows from the short-term versus long-term results.

It seems that intermittent VLCDing helps diabetics in general with glucose control, but is truly curative for those in which enough beta cell function has been preserved. At least this is one explanation for the fact that those with immediate positive results (at the 3-week mark) tend to be the ones who retain those results over the long term.

The immediate positive results may well be due to those individuals not having reached the point at which significant and irreversible beta cell damage occurred. In other words, this study suggests that intermittent VLCDing can be particularly helpful in the long term for prediabetics.

This third, and speculative, conclusion may have to be revisited in light of the excellent discussion by Roy Taylor on the etiology and reversibility of type II diabetes (), linked by Evelyn (see comments under this post). This refers to the effects of an extended and more extreme version of VLCD than discussed here, where uninterrupted VLCD would last as long as 8 weeks.

For those who are not diabetic, I personally think it would be better to alternate VLCD with glycogen depleting exercise (e.g., sprints, weight training), every other day or so, with a lot more food consumed on exercise days (). After excess body fat is lost, it would be advisable to stick to weight-maintenance calorie intake, averaged over a week.


Charles Grashow said...

What about this study on high carb macrobiotic diets for Type 2 diabetes?

Ned Kock said...

Hi Charles. I’d have to look at the study more carefully, but at first glance the results look impressive. The emphasis is on low GI carbs. Note that the body fat loss is statistically significant, likely leading to a significant increase in adiponectin and insulin sensitivity. Also, exercise is presented as an important factor – this is from the article:

“The greatest global effect of the diet was observed in the Italian study and could be explained by the better conditions experienced during the study: patients were located in a hotel close to the sea, had strict controls on food consumption, better food preparation and cooking methods, and a higher level of physical activity ...”

Ned Kock said...

I’ve just noticed one potential problem with the study Charles. Apparently the vast majority of the participants were taking diabetes medication while participating in the study, including some taking insulin. If this is correct, the question then becomes: would the treatment have been as effective if they were not taking medication?

john said...

I don't see how this can be an effective long term strategy. What is going to happen once these people are thin / are no longer losing weight? Unless there is something actually curative occurring, the "improvements" are simply temporary changes coupled to fat loss. Every "diet" "cures" diabetes short term.

Anonymous said...

Bariatric surgery patients are essentially cured of their T2 Diabetes in a matter of days. I think the answer lies in their very restricted caloric intake (especially the days following surgery). Insulin resistance is a (mal)adaptation, and is therefore perfectly reversible under different circumstances, given there has been no permanent damage yet.

Charles Grashow said...

From the study

"The positive effect of the Ma-Pi 2 diet on the glycemic profile and on venous glucose was independent of hypoglycemic drug consumption. Overall, insulin had to be reduced by 50% in all 91 insulin-treated subjects to avoid hypoglycemia: from 2.666 units at onset (29.3 units per person) to 1.335 units at t21 (14.67 units per person). Analysis by country showed that in Cuba, China and Ghana, a similar percentage reduction in insulin was observed (45%), whereas a greater reduction (82%) was demonstrated in the Italian study. The use of hypoglycemic drugs decreased by 39% in Italian patients."

"After 21 days, the mean insulin consumption dropped by 46% (617 units); 3 months later up to 858 units (64%) in relation to onset. The consumption of hypoglycemic pills did not show changes during the first 21 days, while 3 months later it had diminished in 10 pills (17%)."

Total volume of the Ma-Pi 2 diet consisted of 40–50% whole
grains (rice, millet and barley), 30–40% vegetables (carrots, kale,
cabbage, broccoli, chicory, onions, red and white radish, parsley),and 8% legumes (adzuki beans, chickpeas, lentils, black beans), plus gomashio (roasted ground sesame seeds with unrefined sea salt), fermented products (miso, tamari, umeboshi) and seaweeds(kombu, wakame, nori). Bancha tea (tannin-free green tea) was the main source of liquid.

At termination of the intervention, insulin administration had been
eliminated in all patients, and 12 patients (75.0%) were receiving
the Ma-Pi 2 macrobiotic diet as their only therapy. Overall glibenclamide use increased from 6 to 15 tablets daily (0.76
mg/kg weight), since 4 patients initiated glibenclamide
therapy when they stopped taking insulin."

Evelyn aka CarbSane said...

This is a great article by the lead researcher in the Newcastle study.

What is different in these studies vs. some LC interventions is that these people are not doing this forever. Similar results have been seen with early insulin treatment for a matter of a couple of weeks and then a considerable portion remaining diabetes free for 1 to 2 years. Since these are eating carbs, one can truly use terms like "cure" or "reversal" instead of "management" and somewhat misused "remission" with VLCarb diets.

Ned Kock said...

Thanks Evelyn. I edited the post (toward the end), and may write a new one in light of the link you provided.

js290 said...

Blood glucose, while cheap and easy to measure, may not be a good proxy for insulin. As Ron Rosedale likes to point out, "Diabetes is not a disease of blood sugar. It's a disease of insulin signaling." Measuring FPG and A1c may not be the best metrics for determining whether a diet cured diabetes. Insulin response may be a better metric.

Toast Test:
"I had done this to other people, too. I knew that most people who have toast, it’ll cause their insulin to go from maybe a baseline of 5, which is quite good, to maybe the 30s or 40s, which is somewhat high. (Note-This rise happens during a 2-hour test) I measured his insulin level, after he ate a piece of toast, and his insulin levels went into the hundreds."

Anonymous said...

You a word in the first paragraph.
Debate? Discussion?

Stephan Guyenet said...

Interesting article Ned. I wonder what would have happened to a fourth group that received the same kcal intake as the intermittent VLC groups but spread out evenly? I wonder if they would have achieved the same level of glucose control after 20 wks.

I think there may be something to be said for extreme, short-term interventions like this. If I was T2 diabetic, I'd certainly try it. The problem is that you can't really recommend that sort of intervention because it carries too much liability.

Ned Kock said...

Hi Stephan. The link below discusses the effects of more extreme versions of the diet:

I don’t doubt that these more extreme versions can have an acute effect on insulin sensitivity. But I wonder, even if (as Taylor claims) beta cell recovery occurs, whether any overall health improvement really occurs.

Starvation has historically been associated with reduction of degenerative diseases in populations, but also with greater mortality.

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Just want to say your article is as surprising.The clarity in your post is simply spectacular and i can assume you are an expert on this subject.

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