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With the right diet and lifestyle, stem cell treatments, probiotic supplements or xylose-laden "functional foods" wouldn't be necessary in the first place.

You're probably used to it, but I am in the mood for bragging: The waredownloadsoft is where you'll read about the latest nutrition, exercise and supplement related studies first. In research updates like the one today, I am trying to provide a little more information than in the SV Facebook News, though, where I usually stick only to the main results of studies that have just been published or at least accepted for publication.

In today's installment of what I often call the "Short News", I will discuss three papers that are going to be published in one of the next issues of the peer-reviewed scientific journal Nutrition News.

Studies dealing with a pre-clinical, but promising stem cell therapy for diabetics, the verdict on probiotic supplements (including my evaluation of the scientists' verdict ;-) for weight loss and an update on the effects of the xylitol precursor d-xylose and its effect on mammalian fat cells in vivo.

• Stem Cells as Diabetes Treatment (Xing. 2015) - In software development you'd probably call the latest study from the Cangzhou City Central Hospital an "early alpha version" of an intriguing new way of treating type II diabetes.
  
  In their latest rodent study, Baoheng Xing et al. build on previous experiments in which pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice (Kroon. 2008). In their study, however, Xing et al. went one step further and developed a system for treating diabetes using human embryonic stem cell–derived pancreatic endoderm in a mouse model of gestational diabetes mellitus.
  

  Figure 1: Glucose (a), insulin (b) and body weight (c) levels of wild type (wt) and treated (db/+PE) vs. untreated (db/+) pregnant mice before and during gestation, as well as Kaplan-Meier survival curves of litters show significant improvement right into the normal range in response to treatment (Xing. 2015)

  To this ends, the researchers had human embryonic stem cells differentiate in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus.
  
  As the data in Figure 1 goes to show you, the transplant, of which the researchers expect that it could be used in humans, too, greatly improved the glucose metabolism and reproductive outcome of the treated female rats compared with the control groups. With their results Xing et al. do thus contribute to the growing evidence that diabetes may (sooner or later) be a "curable" disease when we are eventually mastering the use of differentiated human embryonic stem cells for treating general and gestational diabetes mellitus patients.
• Probiotics and weight loss - reviewed (Park. 2015): What's the verdict? You will remember that I am still skeptical with respect to the real world benefits of the new en-vogue supplements that contain billions of life or dead bacteria and promise benefits from increased gut health to... you guessed it, the most marketable of all benefits: weight loss!
  
  A recent systematic review by scientists from the Hoseo University and the Keimyung University in Korea presents the first attempt to summarize and critically evaluate the evidence from clinical trials that have tested the effectiveness of probiotics or foods containing probiotics as a treatment for weight loss. Literature searches of electronic databases such as PubMed, Cochrane Library, and EMBASE were conducted. Methodological quality was assessed using body weight and body mass index (BMI). Initial searches yielded 368 articles. Of these, only 9 met the selection criteria. Because of insufficient data, only 4 of the studies were randomized controlled trials (RCTs) that compared the therapeutic efficacy of probiotics with placebo.
  
  As my skepticism would have made me believe, the meta-analysis of these data showed no significant effect of probiotics on body weight and BMI (body weight, n = 196; mean difference, −1.77; 95% confidence interval, −4.84 to 1.29; P = .26; BMI, n = 154; mean difference, 0.77; 95% confidence interval, −0.24 to 1.78; P = .14).
  

  Figure 3: It's not like there were no benefits. You just have to look at the right parameters to see them. Studies like Kadooka et al. show that the effects on BMI are small compared to those on metabolically more relevant markers like total fat mass, waist circumference and visceral fat (Kadooka. 2015).

  That does not mean that there are no benefits at all, though. I reviewed the few studies that measured not just body weight and BMI, but also the subjects' body fat levels. This is an important difference, because a focus on BMI ignores potentially health relevant changes in body composition. Changes as they were observed by Kadooka et al. (2013; see Figure 3), for example, who found a significant time x group differences for visceral fat, fat percentage, fat mass, and waist circumference with much less pronounced effects on BMI (too low to influence the result of a systematic review significantly) in their 12-week study. In this context, it is also worth mentioning that Sanchez et al. (2014) observed a significant beneficial effect in obese women (but not man) for whom the consumption of 1.6 × 10^8 colony-forming units of LPR/capsule with oligofructose and inulin made it significantly easier to maintain their body weight after a weight loss intervention. Another benefit that must not be ignored.

• Overall, I still feel obliged to repeat what I wrote in my recent article on the effects of sweeteners on the microbiome: We still have to learn very much about the effects of probiotics in general and individual types of gut bacteria, in particular, before we can actually give good strain-specific supplement recommendations. It's after all possible that the same strains that work in the obese subjects of studies like Kadooka (2015) won't work or even do the opposite in lean individuals.
• D-Xylose Exerts Epigenetic Anti-Obesity Effects and Stops Fat Cell Growth (Lim. 2015) - Yes, this is not the first study to show that the provision of D-Xylitol or, as in the case of a 2011 study by Amo,et al., its cousin and "artificial sweetener" xylitol can reduce the weight gain due to obesogenic diets. What makes it interesting, though, is that it involved two different, relatively low dosages of D-xylitol as they could easily be added to our own food chain.
  

  Figure 4: While the effects on body weight and fat gain were significant, the differences (expressed relative to the rodents on regular chow) are still significant, so even if you replace 5-10% of the sugar in your junkfood diet with the low calorie sweetener (2.4kcal/g), you will get fat. If anything it may completely prevent the increase in liver fat - albeit only if the dosage is high enough and the effects are identical in humans (data from Lim. 2015)

  With only 5% and 10% of the sucrose content of the high fat chow of the rodents in Lim et al.'s latest study being replaced by D-Xylose, the scientists observed
  • significant reductions in weight and more importantly fat gain
  • significant reductions in hepatic steatosis (NAFLD),
  • a reduction of the genes that are responsible for the storage of fat to normal (5%) and sub-normal (10% D-Xylose) levels, and
  • significant reductions in total cholesterol and low-density lipoprotein cholesterol, low-/high-density lipoprotein, and the important total cholesterol/high-density lipoprotein ratio.
  In view of the fact that replacing just a relatively small amount of sucrose in our diet with D-Xylose (and probably xylitol) can ameliorate the weight and adipose tissue gain, normalize blood glucose levels and blood lipid profiles and lower the lipid accumulation in the liver by "regulating expression of lipogenesis- and β-oxidation–related genes" (Lim. 2015), it is probably actually warranted to speculate, just like Lim et al., about a "possible application of d-xylose as a dietary supplement for the prevention of obesity-related metabolic disorders" (Lim. 2015) - even though clinical human trials are still warranted.

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).
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.

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).
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. 

References:

• 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).