Bump: The Diabetes "Crash" Cure & Pancreatic Fat

Today's 8/15/13 bump was inspired by a comment by Tsimblist (thanks!) alerting me to this paper:  Type 2 Diabetes Etiology and reversibility

Reversal of type 2 diabetes to normal metabolic control by either bariatric surgery or hypocaloric diet allows for the time sequence of underlying pathophysiologic mechanisms to be observed. In reverse order, the same mechanisms are likely to determine the events leading to the onset of hyperglycemia and permit insight into the etiology of type 2 diabetes. Within 7 days of instituting a substantial negative calorie balance by either dietary intervention or bariatric surgery, fasting plasma glucose levels can normalize. This rapid change relates to a substantial fall in liver fat content and return of normal hepatic insulin sensitivity. Over 8 weeks, first phase and maximal rates of insulin secretion steadily return to normal, and this change is in step with steadily decreasing pancreatic fat content.

Read more »

Aug. 1 Over the Hump Bump: Baby your Pancreas? Part I: The Tired Pancreas

Another two-fer for the Thursday post bumps again this week.  More explanation for why this set in the next bump.

---

Original Publish Date:  7/26/11

In the comments on a recent post on beta cell lipotoxicity, Ned Kock (of Health Correlator blog) posted a link to a post he made a while back entitled:  Lipotoxicity or tired pancreas? Abnormal fat metabolism as a possible precondition for type 2 diabetes.  This article deals with the concept of the "tired pancreas" in the development of diabetes.  It seems that (and hopefully he corrects me if I'm wrong here) Ned and I agree that this is not a likely explanation for diabetes.   Ned summarizes the progression of obesity induced T2 diabetes from Unger & Zhou, 2001.  It is worth mentioning that Unger is often summarily dismissed from the "scientific discussion roundtable" by low carbers because of the unfortunately titled "Gluttony and Sloth" paper, that, even more unfortunately also included a biblical verse.   Unger's hypothesis is very leptin-centric, but not at all incompatible with other lipotoxicity based theories.  Basically, lipotoxicity is the result of dysfunctional adipocytes leading to excessive "spill-over" of fatty acids into circulation and accumulation in ectopic tissues.   Unger & Zhou identify dysfunction in leptin secretion and/or signaling as the initiating factor in this process.  One thing that doesn't quite add up for me here is that I keep finding citations indicating leptin action increases free fatty acids which would seem counterintuitive.  In any case ...

Read more »

Laura Dolson on the recent meeting of the American Society of Bariatric Physicians

*** Can you help a girl out?  Where is the traffic coming from?? Thanks! ***

In the past week, I've noticed a sustained trickle of traffic to this post of mine from over a year ago (original publish date 4/28/12) .  Therefore, rather than write another post on a somewhat older topic, I decided to bump this one and add some comments.   For most of this year I have been under attack for posts of this nature and all I can do to counter those is to point out that this post is not a personal attack.  What I've written is as respectful as can be when the subject is someone who, were she promoting veganism or McDougall's diet would be vilified and likely destroyed in the LC community.   Yet I haven't done so even though I believe Laura Dolson is deserved of some criticism for not telling the full story here.

Read more »

Fast or Feltham II

Busy weekend here!  I'm working on a couple of posts, one of which is a closer look at the 5000 calorie/day stunt by Sam Feltham as that provides a context in which to discuss some common CICO strawmen.  But a comment came across the feed reader yesterday that caught my eye with a few more thoughts in the vein of my first Fast or Feltham post. 

I'm not going to say much more about Feltham here except to say that his experiment was basically "nuts".  The majority of his calories (53%) were from walnuts, pecans and almonds, to the tune of a pound a day, containing more than the entire claimed caloric surplus, and almost the full claimed surplus in nut fat calories.  This was a stunt that demonstrated nothing other than that Feltham likely doesn't digest nuts well, and is using this to promote a rip-off of Jonathan Bailor's clogged sink scam.  But stunts like this bring the calorie deniers out of the woodwork as various folks will be like "did you see this?" and link to various other overeating stunts of years gone by.  LCHF is being sold, still, as a diet where calories don't matter, "overeating" is inane, and you can eat thousands of calories more and not gain weight.  

Read more »

The New Paleo Diet Study: Just the Fats Ma'am

A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women

I don't know that this study is worth three posts -- grin -- but I decided to break it up anyway.  I blogged on the diet itself here, and the weight loss here.  This post will address the impact on ectopic fat.  So first, I want to mention the "misleading title" peeves.  Ectopic fat is defined in the abstract:

Ectopic fat accumulation in liver and skeletal muscle may be an essential link between abdominal obesity, insulin resistance and increased risk of cardiovascular disease after menopause.

Here's the relevant synopsis of the results:

Liver triglyceride levels decreased by 49% whereas IMCL [intramyocellular lipid] levels in skeletal muscle were not significantly altered.

Which apparently garnered the conclusion:

A modified Palaeolithic-type diet has strong and tissue-specific effects on ectopic lipid deposition in postmenopausal women.

Read more »

The New Paleo Diet Study: The Weight Loss

I've written previously about the diet used in the latest paleo diet study. In this post I want to address the results.  Here's the study:  A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women.   In this post I am going to address the weight loss (and change in intake) only.

On the "con"side we have the following:

• Small, n=10
• No control group
• Short - 5 weeks

On the "pro" side, there appear to be (see small type below) significant controls in place to ensure compliance, accurate reporting of intake, etc.

Summary:  This group spontaneously decreased caloric intake by an average of 25% with a mean weight loss of 4.5 kg in 5 weeks.  That works out to 2 lbs per week weight loss ... a decent clip.  Two things I would like to highlight:

Read more »

More Hyperinsulinemia, Insulin-Suppressive Drugs & Obesity (and Lustig)

Building on my last post on this topic ...

So far I've spent most of the blogging on a study comparing 3 doses of octreotide, an insulin suppressing drug, vs. placebo in a subset of obese people pre-tested and determined to be insulin hypersecreters as defined by a corrected ratio for insulin to glucose levels.  This post will focus more on two other studies using this drug, perhaps just the first ... let's see how long this gets ;-)    I think it will be easiest to number the 3 studies, all bearing Lustig's name:

• Study 1: Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults (2003)
• Study 2: Obesity, leptin resistance, and the effects of insulin reduction  (2004)
• Study 3: A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion.  (2006)

I've already discussed the rather unimpressive performance of octreotide in Study 3.  While the highest dose group had the highest "response" rate (20.5% losing ≥5% initial weight), the rates were similar between the placebo group (11.4%) compared to the 40mg octreotide group (12.5%), which is important as this is the dose used in Studies 1&2.   Additionally, mean losses for the entire 40 & 60 mg groups were less than 2%, and even the most promising responders, Caucasian hypersecreters with above median CIR, only lost an average of less than 4% over 6 months.

Read more »

Ketosis and Burning Body Fat

Alternate Title:  Picture Worth More Than 1000 Words.  In speeches and interviews lately, Jimmy Moore has become fond of mentioning a few things (well, in addition to name dropping Robb Wolf)

• Nutritional Ketosis as being somehow unique from run-of-the-mill, what, biochemical ketosis.  NK requires blood ketone testing as this is more accurate.  And,
• Ketosis is evidence of burning body fat which he wasn't doing prior to this experiment.
• Ketones and blood glucose being reciprocal

Tis true that measuring blood ketone levels is more accurate than urine ketones.  For one thing, urine levels vary widely with fluid intake, frequency of urination, etc.  Urine ketones are also "spill-over".  This is why nobody is ever busted for DUI on the basis of a urine test.  But just because urine levels are not necessarily representative of one's ketogenic production doesn't mean a person is, or is not, in NuttyK.  But let's presume that to be truly NuttyK one must also be a prick-er.  

On the right sidebar are Jimmy's NuttyK experiment results from Days 180-209.  Top to bottom we have AM glucose, AM ketones, PM ketones,  and body weight.  Do YOU notice any correlation?   Here's what I see:

Read more »

Hyperinsulinemia, Insulin-Suppressive Drugs & Obesity (and Lustig)

The recent buzz about hyperinsulinemia being at the root of obesity (whatever the mechanism) has had me thinking again about the insulin lowering drugs.   Studies in this regard were referenced in the recent article in Cell from Dr. James Johnson's research group at UBC.   If this is really all there is to it, why not just treat obesity with such drugs?  Or at least give them to the reduced-obese so they won't regain the weight, and/or the so-called pre-obese who start gaining at some point in life before they become obese.  This is really the bottom line of studies like the recent one from UBC.  Because if all we need to do is suppress the hyperinsulinemia (however it is caused) to prevent obesity it would be done.  There is a relatively rare condition, called by many names, but most descriptively neo-natal or infant hyperinsulinism.  These children must be treated ASAP to avoid the consequences of hypoglycemic episodes.  I surmise the drugs octreotide and diazoxide were developed at least in part for treating this condition, though often partial removal of the pancreas is required.

Read more »

Some downplayed and/or ignored revelations from Shai

link, click to enlarge

This will be a relatively short post, but due to my recent offering, I re-read some of the original Shai et.al LF v. Mediterranean v. LC diet comparison study and had some commentary to add.  First, leaving aside reasons for withdrawal, there was a significant difference in compliance/completion between the three groups -- roughly 90% of LF, 85% of MDTN and 78% of LC subjects that completed the 2-year intervention.  

Read more »

Mashed Sous Veades Low Carb Logic

Well, the pudgy mirdled one, diet book author and former diet doctor Mike Eades has taken a break from changing the world** with his Sous Vide* to compose his ninth blog post of the year!  Last we heard from him here at The Asylum, he and his wife had resolved to -- yet again! -- diet in 2012.  You'll see why all of those links are relevant as we get into discussing his latest:  Are carbohydrates fattening?

His post refers to the 6 year follow-up (4 years after the initial 2 year study) from the famous diet comparison study from Shai et.al.  I discussed this study back in my more gregarious days (grin) in Gary Taube$, Shai-ster?   This study was done in a workplace setting in Israel, where through the cafeteria, they were able to assist participants in complying with the diet by offering choices labeled as appropriate for their assigned diet plan.  

In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index..., 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non–restricted-calorie.

Lest there be any confusion as to how the diets were prescribed, here is that section from the original paper:

Read more »

Amazing (and Not So Amazing) Low Carb Feats

Preface:  When I write posts such as this one, that I know some will take in ways in which it was not intended, I usually spend a bit of time contemplating hitting the publish button.  This post comes off rather more wet blankety (is that a term?) than even some others.   But as someone who has struggled with the after effects of yo-yoing, LC and not, I do think it is worthwhile to shine a light on the reality of what is being promoted out there.

Read more »

More on Look AHEAD

Thanks to the many readers who supplied links and additional information in comments on my last post on that diabetes study run amok (grin).  

LookAHEADTrial.org website , Study protocol , Four Year Followup

Phase I = First Year:   Lifestyle Intervention [subjects] will be seen four times per month (three group sessions and one individualized session) for six months and then twice per month for six months, with an opportunity for more frequent follow-up. The goal will be to induce a 7-10% weight loss and to increase exercise to 175 minutes per week. Participants assigned to Diabetes Support and Education will be offered three educational/support sessions. 

Only the first year was intended to be a weight loss phase.   

Read more »

That diabetes study that ended early ...

Did you hear?  From the New York Times last week:  Diabetes Study Ends Early With a Surprising Result.  Thus far there's been some of the usual responses from the low carb community, and I expect more to come.  For starters, the writer is Gina Kolata, a woman reviled by Gary Taubes and thus his adoring fans, so we'll get the usual round up of Gina doesn't get it that low carb is the bestest and only way to treat diabetes ... duh!!   Let's look a bit closer, shall we?  

First, keep in mind this study has not been published up, so we're dealing with press releases and quotes here.  Secondly, ending the study early makes it sound quite a bit more dire than what we know to have happened.  The study was apparently to last 13 years (odd duration, that), but was ended at 11 years because no differences were seen between the study and control groups over that time.  Sounds prudent, because likely they looked at the numbers and probably concluded that there would need to be an unfathomable number of incidents/deaths in the remaining two years to alter the results.  Save the money.  Good.

Read more »

Weight Loss Celebs & Credibility

I’ve read that [he] has regained quite a bit of the weight. When I’ve seen him [in pictures] lately, it’s only from the shoulders up.

Questions:

1. Who is "he"?
2. Who said this?
3. What is he/she implying about the subject?

Read more »

NuSI ... or Just Do It!

Imagine if you will, that a decade or more ago someone told you that if you really wanted to build your journalism career tearing down scientists, you needed to look at diet and nutrition research.  You picked up a copy of Atkins and lost a couple of pounds.  You began cultivating your schtick that simple obesity (the kind of the epidemic) was not about overeating or sedentary behavior, it was something else.  And you received three-quarters of a million dollars to research and write a book.  The book was a best seller and garnered you a cult following in certain circles and you were off to the races giving talks around the globe.  

There were doctors and others who bought into your hypothesis, spreading the word as fact and growing the movement.  But a following from one segment of the population remained elusive:  scientists.   Rather than address the reasons why (serious holes in your hypothesis), you double down and trash scientists more openly and frequently.  You also publish a second book with a dumbed down, even less scientific, hypothesis.  By all indications, this book falls far short of expectations ... and still the scientists are not coming around.  Worse still, many who had believed your hypothesis was plausible, at least worthy of investigation, were abandoning it.

Read more »

What we really learn from Ebbeling et.al.

I think Kevin Hall's observation that the TEE's measured in the supposedly weight stable phase of this diet, that varied from an average of 140 to >500 cal/day more than the average intake pretty much negates drawing any sort of meaningful conclusions from the  Ebbeling et.al. study.  It really is a waste of time and mental energy to discuss a highly suspect 300 cal/day difference in TEE measured by state of the art methods, but highly susceptible to error as it was not measured directly.

But what can we learn from this study?  Well, as with the Biggest Loser study we learn that:

Read more »

A Friday JAMA-lama Ding Dong!

Well ... I wasn't really going to weigh in further past using that recent JAMA article (EDIT:  full text no longer free at JAMA, see link below) as an example of where statistics can lead us astray.  But ... as is probably expected, this study has kicked up some dust in the community.  I'm sure I'll miss a few, but here's the weighing in so far:

Stephan Guyenet

Anthony Colpo

Marion Nestle

Don Matesz

Fat Head

That's just the blog posts, not the tweets, FB postings or other social media buzz ... and I'm happy to edit in more, just drop the hint in comments.  And here's the full text of the study:  Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance

Read more »

More on the latest LC/LF Diet Comparison Study, and Why LF & CRD's "fail"?

I thought of just updating the last post, but this is long enough on its own to warrant a Part II of sorts.  If you haven't read it yet, may I suggest:  LC v. LF Diet Comparison Study Shows Calories Determine Weight Loss.  What distinguished this study from many other comparison studies, was that there was an attempt at keeping calories constant between the diets.  Usually LC is ad libitum, which, especially the first time one follows a low carb diet, tends to substantially spontaneously reduce caloric intake more than what is generally prescribed for a "responsible" calorie restricted diet (CRD).  This was also a longer term study and also compared two different fixed prescribed diets rather than the usual Atkins-style induction/progression formula.  Presuming compliance, then, the study controlled for calories and sought to look at the effects of just the macronutrient composition of the diet.  

In my opinion, the rather negligible differences for both groups after a year and continuing through two years show that neither dietary intervention was particularly effective, resulting in under 10 lbs weight loss and only transient improvements in HbA1c as measured by one method only.   So why was that?  Well, the prescribed caloric intake was fixed at 1600 cal/day for women and 1800 cal/day for the men.  Right there this part of the study design pretty much doomed it to failure.  While men generally have higher caloric needs than women, total daily energy expenditure varies so widely between individuals that clearly some women have higher needs than some men, and some men and women have higher needs than others of their gender.

Read more »

Conjugated Linoleic Acid (CLA) ~ Good or Bad?

While I was looking at something unrelated (except that it was a fatty acid), the following popped up in my search:  Weight loss supplement - conjugated linoleic acid - shows nasty side effects.  Conjugated linoleic acid (CLA) first came to my attention, other than hearing about it as a supplement from time to time, during a discussion on trans fats and trans fat content of certain foods.  CLA is a trans fat, it's just not an unnatural nasty chemical we associate with the term these days.  It's found in meat of grassfed animals in particular, milk/dairy from same animals and eggs.   If you do a search on CLA and trans fat you'll turn up all manner of reports how it's the "good" or "healthy" trans fat.  In addition to some anti-cancer claims, it's also touted as the "belly busting" trans fat.  Sign me up!  

But, not so fast according to the article, which references two studies: (2007, nothing new here, just thought I'd pass this along as I hear buzz over CLA from time to time)

Read more »