Saturday, November 14, 2015

World Diabetes Day: Is Bariatric Surgery the Only Tool to Send T2DM into Remission? Adherence to 6 Months of Daily Exercise and Eating 500kcal/day Less Works, Too!

Diabetes is a disease that is currently often only managed, not treated and that despite the fact that scientists know ways to send T2DM it into remission.
With the 14th of November being the World Diabetes Day, I thought it may be worth taking a look at the available evidence on treating, not just managing diabetes. If you do just that, there is one treatment that sticks out: Bariatric surgery.

There is currently little doubt that weight loss surgery is the most promising tool doctors have to actually "treat" type II diabetes. As Esposito et al. point out in their recent review of the literature,  "more information is [however] needed about the long-term durability of comorbidity control and complications after bariatric procedures" (Esposito. 2015).
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Why's that? Well, while the review which comprised three randomized controlled trials and one prospective study that compared the effect of Roux-en-Y gastric bypass (RYGB) procedure against optimal medical therapy, shows that the percentage of diabetic patients in remission (hemoglobin A1C < 6–6.5 % without medications) ranged from 38 to 75 % at the end of follow-up, the large inter-individual differences and the fact that the same review also says that
"[i]ntensive lifestyle intervention is also superior to conventional treatment for inducing remission of type 2 diabetes, with remission rates of type 2 diabetes between 10 and 15 % at 1 year of follow-up" (Esposito. 2015), 
it appears to me as if it was more than worthwhile to highlight that (a) surgery is not the only tool and (b) it is not a reliable method to help people regain control over their health. In fact, it is not the surgery but what happens afterwards that determines ultimate success and here, studies show the same factors to determine between failure and success that would make weight loss surgery obsolete for many non-extremely-obese type II diabetics in the first place. Which factors that would be? Here is a selection that was compiled by Elfhag and Rössner in 2005, already:
Table 1: Factors associated with weight loss maintenance and weight regain after intentional weight loss according to a literature review (Elfhag & Rössner. 2005)
You're seeing patterns you don't observe (left hand) or do observe (right hand side of Table 1) in your type II diabetic uncle or aunt? Well that's certainly no coincidence. The results Elfhag & Rössner published published in 2003 have been repeatedly confirmed.

Figure 1: If you look at the relatively low number of subjects who weren't able to maintain at least 50% of their weight loss, it should become obvious that at least within the first year RYGB surgery is not as black as it is painted by some critics (Cooper. 2015).
Nevertheless, more recent research such as a 2009 study by Odom et al. are useful because they (a) quantify known risk factors and add new ones:

  • Food urges is associated with a 5.1x increased risk of weight regain.
  • Not feeling that the surgery has improved ones life is linked to a 21.5x increased risk.
  • Alcohol or drug use is associated with a 12.74x increased risk.
Against those figures, the 6% reduced risk of significant weight gain  in those with lower scores on a test for depression Odom et al. observed in their analysis of the data appears to be of surprisingly minor practical significance.
After sign. weight loss beta-cells can be "resurrected". Meaning they will undergo a process of apoptosis, death and regeneration (Su. 2015).
But isn't the damage already done? While the damage is done, recent research clearly indicates that once the excess weight and with it the chronic hyperglycaemia, hyperlipidaemia and/or cytokines are gone, the damaged beta-cells "undergo the process of rebirth, which involves apoptosis evasion, regeneration and improved beta-cell function" (Su. 2015). While Su et al. point out that the research is not far enough to copy the effects with a drug, it is yet far enough to say that weight loss surgery works and that's what matters, no?
Self monitoring, on the other hand, doesn't only cut the risk of significant weight gain by 46% and is thus practically relevant, it is also in line with the notion of "being willing and able to do what it takes" that emerges from is the gist of the items on the list Elfhag & Rössner compiled back in 2005.

So what does it take, then?

Self-monitoring is yet only one of the points on the "it takes all this"-list you would have to hand somebody who wants to send his type II diabetes into remission. The be-all and end-all for >90% of the type II diabetics is - even if you are constantly bombarded with opposing messages - the induction of a negative energy balance of which studies Malandrucco et al., who put 14 severely obese type II diabetics on  very low calorie diet (400kcal /day), show improvements in beta cell function after only 7 days! These are experimental results epidemiologists with their "people are not eating too much and moving too little, there must be another reason we are fat"-bogus will have a hard time to debate.
Figure 2: The amount of overweight lost is the only significant predictor of remission of remission of type 2 diabetes mellitus (T2DM) after gastric bypass in a cohort of 177 patients with T2DM who had undergone Roux-en-Y gastric bypass from 1993 to 2003 had 5-year follow-up data available (Chikunguwo. 2010).
I won't negate that there are corollary effects such as changes in satiety hormone production, the new found ability to exercise (let's be honest, with lean and muscular 150lbs it's cheap to say that someone who weighs 500lbs is just too lazy to work out - at that weight he, let alone she, is simply unable to work out!), the motivation that comes with the first visible results and so on and so forth. When all is said and done, though, studies show that "[w]eight regain [is the only] statistically significant, but weak predictor, of T2DM recurrence" after weight loss surgery (Chikunguwo. 2010).
There's more than just one study showing that lifestyle changes alone can reverse type II diabetes! Partial or complete remission of diabetes, defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia (fasting plasma glucose <126 mg/dL and hemoglobin A1c <6.5% with no antihyperglycemic medication) can be achieved only, though, if the intervention triggers significant weight loss and improvements in fitness levels. That's what a 2012 review in JAMA shows. With the -7.9% extra weight loss and the +6.4% extra increase in fitness, subjects who participated in intense lifestyle interventions were 6x more likely to achieve remission than those who participated in the typical "you should eat more healthy and do some cardio"-bogus studies. With a remission rate of 11.5% in the first and 7.3% after four years, Gregg's review does yet support the previously highlighted need of determination and consistency.
In the previously cited study by Chikunguwo, for example the subjects who achieved diabetes remission had lost on average 70% of their excess weight. Those who failed to normalize their blood glucose management, still hat ~50% of their overweight on their hips. That long-term success is determined by weight loss, not the often cited changes in satiety hormone production that occur in response to the surgery is also supported by several reviewers. Gumps et al. (2005) for example state that
  1. "Metabolic damage" may make it harder, but not impossible for "reduced obese" individuals to stay lean | learn more
    All forms of weight loss surgery lead to caloric restriction, weight loss, decrease in fat mass and improvement in T2DM. 
  2. Improvements in glucose metabolism and insulin resistance following bariatric surgery result in the short-term from decreased stimulation of the entero-insular axis by decreased caloric intake. 
  3. In the long-term by decreased fat mass and resulting changes in release of adipocytokines. 
It should and that's the logical and scientifically confirmed conclusion one can draw based on the previously presented facts, thus be possible to see the same beneficial effects that have been observed in many after weight loss surgery in the selected few who manage to lose their weight by "simply" turning their lifestyles' upside down.

Only recently, Philip A. Ades and colleagues from the University of Vermont Medical Center reported in a paper in the Journal of Cardiopulmonary Rehabilitation & Prevention that partial remission of type II diabetes can be achieved within only 6 months if the subjects were willing to participate in a formal lifestyle program that helped them to lose 7.3kg of fat mass (9.7kg total weight loss | see Figure 3 in the bottom-line). The cornerstones of this program, however, won't make every type II diabetic happy. It didn't just involve a 500kcal/day deficit, but also an "almost daily" exercise program consisting of "high-caloric expenditure exercise," with 1 to 3, 45- to 60-minute sessions per week of supervised on-site exercise and home walking on other days for a total of 5 to 6 days per week of exercise.
Figure 3: If a given life-style intervention facilitates high enough rates of fat loss, remission to tolerable HbA1c levels (see dashed line in small graph) occurs in more than half of the subjects (Ades. 2015).
Type II diabetes is treatable! That's the good news. The bad news is that the only treatment that doesn't require the same efforts people were not willing to go through in the years over which they acquired one extra-pound of body fat after the other is bariatric surgery. And even here, only those who are really willing to make a change have a good chance of reversing type II diabetes.

An alternative, in form of an intense diet + exercise lifestyle intervention exists; and while it may take longer to work, remission rates should border zero for all of those who understand that they cannot return to their previous diet and activity levels. Now I will leave it up to you to decide whether that's a good or bad news on "World Diabetes Day" | Let me and others know what you think and comment!
  • Ades, Philip A., et al. "Remission of recently diagnosed type 2 diabetes mellitus with weight loss and exercise." Journal of cardiopulmonary rehabilitation and prevention 35.3 (2015): 193-197.
  • Chikunguwo, Silas M., et al. "Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric bypass." Surgery for Obesity and Related Diseases 6.3 (2010): 254-259.
  • Cooper, Timothy C., et al. "Trends in weight regain following roux-en-Y gastric bypass (RYGB) bariatric surgery." Obesity surgery (2015): 1-8.
  • Elfhag, K., and S. Rössner. "Who succeeds in maintaining weight loss? A conceptual review of factors associated with weight loss maintenance and weight regain." Obesity reviews 6.1 (2005): 67-85.
  • Esposito, Katherine, et al. "Remission of type 2 diabetes: is bariatric surgery ready for prime time?." Endocrine 48.2 (2015): 417-421.
  • Gregg, Edward W., et al. "Association of an intensive lifestyle intervention with remission of type 2 diabetes." Jama 308.23 (2012): 2489-2496.
  • Gumbs, Andrew A., Irvin M. Modlin, and Garth H. Ballantyne. "Changes in insulin resistance following bariatric surgery: role of caloric restriction and weight loss." Obesity surgery 15.4 (2005): 462-473.
  • Malandrucco, Ilaria, et al. "Very-low-calorie diet: a quick therapeutic tool to improve β cell function in morbidly obese patients with type 2 diabetes." The American journal of clinical nutrition 95.3 (2012): 609-613.
  • Su, Yinjie, Yanling Zhao, and Chaojun Zhang. "Bariatric surgery: beta cells in type 2 diabetes remission." Diabetes/metabolism research and reviews (2015).